Module 16: The Urinary System

Lesson 5: Renal Clearance, Renal Blood Flow, and Glomerular Filtration Rate

Độ Thanh Thải, Lưu Lượng Máu Thận, Và Độ Lọc Cầu Thận

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Dưới đây là danh sách những thuật ngữ Y khoa của module The Urinary System.
Khái quát được số lượng thuật ngữ sẽ xuất hiện trong bài đọc và nghe sẽ giúp bạn thoải mái tiêu thụ nội dung hơn. Sau khi hoàn thành nội dung đọc và nghe, bạn hãy quay lại đây và luyện tập (practice) để quen dần các thuật ngữ này. Đừng ép bản thân phải nhớ các thuật ngữ này vội vì bạn sẽ gặp và ôn lại danh sách này trong những bài học (lesson) khác của cùng một module.

Medical Terminology: The Urinary System

anatomical sphincter
smooth or skeletal muscle surrounding the lumen of a vessel or hollow organ that can restrict flow when contracted
angiotensin I
protein produced by the enzymatic action of renin on angiotensinogen; inactive precursor of angiotensin II
angiotensin II
protein produced by the enzymatic action of ACE on inactive angiotensin I; actively causes vasoconstriction and stimulates aldosterone release by the adrenal cortex
angiotensin-converting enzyme (ACE)
enzyme produced by the lungs that catalyzes the reaction of inactive angiotensin I into active angiotensin II
angiotensinogen
inactive protein in the circulation produced by the liver; precursor of angiotensin I; must be modified by the enzymes renin and ACE to be activated
anuria
absence of urine produced; production of 50 mL or less per day
aquaporin
protein-forming water channels through the lipid bilayer of the cell; allows water to cross; activation in the collecting ducts is under the control of ADH
Bowman’s capsule
cup-shaped sack lined by a simple squamous epithelium (parietal surface) and specialized cells called podocytes (visceral surface) that participate in the filtration process; receives the filtrate which then passes on to the PCTs
brush border
formed by microvilli on the surface of certain cuboidal cells; in the kidney it is found in the PCT; increases surface area for absorption in the kidney
calyces
cup-like structures receiving urine from the collecting ducts where it passes on to the renal pelvis and ureter
cortical nephrons
nephrons with loops of Henle that do not extend into the renal medulla
countercurrent multiplier system
involves the descending and ascending loops of Henle directing forming urine in opposing directions to create a concentration gradient when combined with variable permeability and sodium pumping
detrusor muscle
smooth muscle in the bladder wall; fibers run in all directions to reduce the size of the organ when emptying it of urine
distal convoluted tubules
portions of the nephron distal to the loop of Henle that receive hyposmotic filtrate from the loop of Henle and empty into collecting ducts
diuretic
compound that increases urine output, leading to decreased water conservation
efferent arteriole
arteriole carrying blood from the glomerulus to the capillary beds around the convoluted tubules and loop of Henle; portion of the portal system
endothelins
group of vasoconstrictive, 21-amino acid peptides; produced by endothelial cells of the renal blood vessels, mesangial cells, and cells of the DCT
external urinary sphincter
skeletal muscle; must be relaxed consciously to void urine
fenestrations
small windows through a cell, allowing rapid filtration based on size; formed in such a way as to allow substances to cross through a cell without mixing with cell contents
filtration slits
formed by pedicels of podocytes; substances filter between the pedicels based on size
forming urine
filtrate undergoing modifications through secretion and reabsorption before true urine is produced
glomerular filtration rate (GFR)
rate of renal filtration
glomerulus
tuft of capillaries surrounded by Bowman’s capsule; filters the blood based on size
glycosuria
presence of glucose in the urine; caused by high blood glucose levels that exceed the ability of the kidneys to reabsorb the glucose; usually the result of untreated or poorly controlled diabetes mellitus
incontinence
loss of ability to control micturition
intercalated cell
specialized cell of the collecting ducts that secrete or absorb acid or bicarbonate; important in acid–base balance
internal urinary sphincter
smooth muscle at the juncture of the bladder and urethra; relaxes as the bladder fills to allow urine into the urethra
inulin
plant polysaccharide injected to determine GFR; is neither secreted nor absorbed by the kidney, so its appearance in the urine is directly proportional to its filtration rate
juxtaglomerular apparatus (JGA)
located at the juncture of the DCT and the afferent and efferent arterioles of the glomerulus; plays a role in the regulation of renal blood flow and GFR
juxtaglomerular cell
modified smooth muscle cells of the afferent arteriole; secretes renin in response to a drop in blood pressure
juxtamedullary nephrons
nephrons adjacent to the border of the cortex and medulla with loops of Henle that extend into the renal medulla
leaky tight junctions
tight junctions in which the sealing strands of proteins between the membranes of adjacent cells are fewer in number and incomplete; allows limited intercellular movement of solvent and solutes
leukocyte esterase
enzyme produced by leukocytes that can be detected in the urine and that serves as an indirect indicator of urinary tract infection
loop of Henle
descending and ascending portions between the proximal and distal convoluted tubules; those of cortical nephrons do not extend into the medulla, whereas those of juxtamedullary nephrons do extend into the medulla
macula densa
cells found in the part of the DCT forming the JGA; sense Na+ concentration in the forming urine
medulla
inner region of kidney containing the renal pyramids
mesangial
contractile cells found in the glomerulus; can contract or relax to regulate filtration rate
micturition
also called urination or voiding
myogenic mechanism
mechanism by which smooth muscle responds to stretch by contracting; an increase in blood pressure causes vasoconstriction and a decrease in blood pressure causes vasodilation so that blood flow downstream remains steady
nephrons
functional units of the kidney that carry out all filtration and modification to produce urine; consist of renal corpuscles, proximal and distal convoluted tubules, and descending and ascending loops of Henle; drain into collecting ducts
net filtration pressure (NFP)
pressure of fluid across the glomerulus; calculated by taking the hydrostatic pressure of the capillary and subtracting the colloid osmotic pressure of the blood and the hydrostatic pressure of Bowman’s capsule
oliguria
below normal urine production of 400–500 mL/day
osteomalacia
softening of bones due to a lack of mineralization with calcium and phosphate; most often due to lack of vitamin D; in children, osteomalacia is termed rickets; not to be confused with osteoporosis
pedicels
finger-like projections of podocytes surrounding glomerular capillaries; interdigitate to form a filtration membrane
peritubular capillaries
second capillary bed of the renal portal system; surround the proximal and distal convoluted tubules; associated with the vasa recta
physiological sphincter
sphincter consisting of circular smooth muscle indistinguishable from adjacent muscle but possessing differential innervations, permitting its function as a sphincter; structurally weak
podocytes
cells forming finger-like processes; form the visceral layer of Bowman’s capsule; pedicels of the podocytes interdigitate to form a filtration membrane
polyuria
urine production in excess of 2.5 L/day; may be caused by diabetes insipidus, diabetes mellitus, or excessive use of diuretics
principal cell
found in collecting ducts and possess channels for the recovery or loss of sodium and potassium; under the control of aldosterone; also have aquaporin channels under ADH control to regulate recovery of water
proximal convoluted tubules (PCTs)
tortuous tubules receiving filtrate from Bowman’s capsule; most active part of the nephron in reabsorption and secretion
renal columns
extensions of the renal cortex into the renal medulla; separates the renal pyramids; contains blood vessels and connective tissues
renal corpuscle
consists of the glomerulus and Bowman’s capsule
renal cortex
outer part of kidney containing all of the nephrons; some nephrons have loops of Henle extending into the medulla
renal fat pad
adipose tissue between the renal fascia and the renal capsule that provides protective cushioning to the kidney
renal hilum
recessed medial area of the kidney through which the renal artery, renal vein, ureters, lymphatics, and nerves pass
renal papillae
medullary area of the renal pyramids where collecting ducts empty urine into the minor calyces
renal pyramids
six to eight cone-shaped tissues in the medulla of the kidney containing collecting ducts and the loops of Henle of juxtamedullary nephrons
renin
enzyme produced by juxtaglomerular cells in response to decreased blood pressure or sympathetic nervous activity; catalyzes the conversion of angiotensinogen into angiotensin I
retroperitoneal
behind the peritoneum; in the case of the kidney and ureters, between the parietal peritoneum and the abdominal wall
sacral micturition center
group of neurons in the sacral region of the spinal cord that controls urination; acts reflexively unless its action is modified by higher brain centers to allow voluntary urination
specific gravity
weight of a liquid compared to pure water, which has a specific gravity of 1.0; any solute added to water will increase its specific gravity
systemic edema
increased fluid retention in the interstitial spaces and cells of the body; can be seen as swelling over large areas of the body, particularly the lower extremities
trigone
area at the base of the bladder marked by the two ureters in the posterior–lateral aspect and the urethral orifice in the anterior aspect oriented like points on a triangle
tubuloglomerular feedback
feedback mechanism involving the JGA; macula densa cells monitor Na+ concentration in the terminal portion of the ascending loop of Henle and act to cause vasoconstriction or vasodilation of afferent and efferent arterioles to alter GFR
urethra
transports urine from the bladder to the outside environment
urinalysis
analysis of urine to diagnose disease
urochrome
heme-derived pigment that imparts the typical yellow color of urine
vasa recta
branches of the efferent arterioles that parallel the course of the loops of Henle and are continuous with the peritubular capillaries; with the glomerulus, form a portal system
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The clearance equation is a fundamental equation used in renal physiology to measure the efficiency of renal clearance of a substance. Clearance refers to the volume of plasma from which a substance is completely removed by the kidneys per unit of time. It provides an estimation of how effectively the kidneys can eliminate a particular substance from the body.

The clearance equation is represented as C = U x V/P, where C is the clearance, U is the urine concentration of the substance, V is the urine volume per unit of time, and P is the plasma concentration of the substance. The units of clearance are typically expressed in milliliters per minute (mL/min) or milliliters per 24 hours (mL/24 hours).

The equation essentially calculates the rate at which a substance is excreted in the urine by comparing the urine concentration and volume to the plasma concentration. If the clearance value is high, it indicates that the substance is efficiently eliminated by the kidneys, while a low clearance value suggests poor renal elimination.

The clearance equation is commonly used in clinical settings to assess renal function and to determine the rate of drug clearance. It provides valuable information about the ability of the kidneys to filter, reabsorb, or secrete a specific substance. By measuring the clearance of certain markers, such as inulin or creatinine, clinicians can estimate the glomerular filtration rate (GFR) and evaluate overall kidney function.
Renal blood flow (RBF) refers to the amount of blood that the kidneys receive over a period of time and it represents approximately 25% of the cardiac output, demonstrating the high metabolic demands of renal tissue. The rate of RBF is directly proportional to the pressure difference between the renal artery and the renal vein, and inversely proportional to the resistance in the renal vasculature. Changes in renal vascular resistance can significantly impact RBF.

The regulation of RBF involves both vasoconstrictor and vasodilator mechanisms. Activation of the sympathetic nervous system and angiotensin II cause vasoconstriction of renal arterioles, reducing RBF. Angiotensin II preferentially constricts efferent arterioles, protecting the glomerular filtration rate (GFR) by maintaining an appropriate pressure gradient. Conversely, prostaglandins, bradykinin, nitric oxide, dopamine, and atrial natriuretic peptide (ANP) promote vasodilation of renal arterioles, increasing RBF.

Autoregulation mechanisms ensure a relatively constant RBF despite changes in arterial pressure. The myogenic mechanism involves the contraction of renal afferent arterioles in response to increased stretch, regulating resistance and maintaining blood flow. Tubuloglomerular feedback occurs when increased renal arterial pressure leads to increased fluid delivery to the macula densa. The macula densa senses the load and causes constriction of the adjacent afferent arteriole, compensating for the increased pressure and preserving RBF.

Measurement of renal plasma flow (RPF) is achieved by the clearance of para-aminohippuric acid (PAH). PAH is filtered and secreted by the renal tubules, allowing its clearance to be used as an indicator of RPF. The formula for calculating RPF using the clearance of PAH involves the urine concentration of PAH, urine flow rate, and plasma concentration of PAH. However, it is important to note that PAH clearance underestimates true RPF by approximately 10%, as it does not account for regions of the kidney that do not filter or secrete PAH, such as adipose tissue.

To calculate RBF, RPF is divided by the fraction of blood volume occupied by plasma, which is represented by the term 1 – hematocrit. This adjustment accounts for the fact that hematocrit represents the fraction of blood volume occupied by red blood cells, and RBF is measured in terms of plasma flow. This equation provides an estimation of RBF, which is a vital parameter in assessing renal function and hemodynamics.
Glomerular filtration rate (GFR) represents the rate at which plasma is filtered through the glomerular capillaries into the Bowman’s space per unit of time. Determination of the GFR is one of the tools used to assess the kidney’s excretory function. This is more than just an academic exercise. Since many drugs are excreted in the urine, a decline in renal function can lead to toxic accumulations. Additionally, administration of appropriate drug dosages for those drugs primarily excreted by the kidney requires an accurate assessment of GFR.

A. Calculating the GFR by Starling Equation

GFR is determined by the net ultrafiltration pressure across the glomerular capillaries. The Starling equation provides a mathematical representation of GFR, taking into account various pressures involved in glomerular filtration.

The glomerular barrier, consisting of the capillary endothelium, basement membrane, and filtration slits of the podocytes, plays a crucial role in regulating filtration. Anionic glycoproteins within the barrier limit the filtration of plasma proteins due to their negative charge. In certain glomerular diseases, these anionic charges may be disrupted, resulting in proteinuria.

The components of the Starling equation include glomerular capillary hydrostatic pressure (PGC), Bowman space hydrostatic pressure (PBS), glomerular capillary oncotic pressure (pGC), and Bowman space oncotic pressure (pBS). PGC is the pressure within the glomerular capillaries and remains relatively constant along their length. It can be increased by dilation of the afferent arteriole or constriction of the efferent arteriole, leading to an increase in net ultrafiltration pressure and subsequently GFR. PBS represents the pressure within the Bowman space and is influenced by factors such as constriction of the ureters. Increases in PBS cause a decrease in net ultrafiltration pressure and GFR.

GFR = Kf x [(PGC – PBS) – (pGC – pBS)]
Kf: Filtration coeficient

pGC is the oncotic pressure within the glomerular capillaries and normally increases along the length of the capillary due to filtration of water, leading to an increase in protein concentration. Increases in pGC result from higher protein concentrations and lead to a decrease in net ultrafiltration pressure and GFR. On the other hand, pBS, the oncotic pressure within the Bowman space, is typically negligible and disregarded since only a small amount of protein is usually filtered.

B. Estimating the GFR by Substances

GFR can be estimated closely by intravenous administration of inulin. Inulin is a plant polysaccharide that is neither reabsorbed nor secreted by the kidney. Its appearance in the urine is directly proportional to the rate at which it is filtered by the renal corpuscle. However, since measuring inulin clearance is cumbersome in the clinical setting, most often, the GFR is estimated by measuring naturally occurring creatinine, a protein-derived molecule produced by muscle metabolism that is not reabsorbed and only slightly secreted by the nephron. The estimation of GFR can also be derived from the levels of blood urea nitrogen (BUN). Both BUN and serum creatinine levels increase when GFR decreases. In conditions of hypovolemia, such as prerenal azotemia, the increase in BUN is more pronounced compared to serum creatinine, resulting in an elevated BUN/creatinine ratio. It is important to note that GFR tends to decrease with age due to a decline in renal function, although serum creatinine levels may remain relatively stable due to age-related changes in muscle mass.

GFR = Clearance [Inulin] = U[inulin] x V/P[inulin]
U[inulin]: urine concentration of inulin
V: urine flow rate (mL/min)
P[inulin]: plasma concentration of inulin

The filtration fraction represents the proportion of renal plasma flow (RPF) that undergoes filtration in the glomerular capillaries. It is calculated by dividing the GFR by the RPF. The typical filtration fraction is around 0.20, indicating that approximately 20% of the RPF is filtered. The remaining 80% exits the glomerular capillaries through the efferent arterioles and enters the peritubular capillary circulation. Alterations in the filtration fraction can have significant effects on renal function. Increased filtration fraction results in higher protein concentration in the peritubular capillaries, leading to enhanced reabsorption in the proximal tubule. Conversely, decreased filtration fraction leads to lower protein concentration in the peritubular capillaries, which reduces reabsorption in the proximal tubule.
Changes in various factors in Starling equation can have significant effects on glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction. These changes highlight the intricate balance between pressures and flows within the kidneys.

For instance, constriction of the afferent arteriole, such as through sympathetic activation, leads to a decrease in GFR due to reduced glomerular capillary hydrostatic pressure (PGC). The decrease in GFR is accompanied by a decrease in RPF, but there is no change in filtration fraction.

In contrast, constriction of the efferent arteriole, as seen with the action of angiotensin II, causes an increase in GFR by increasing PGC. However, RPF decreases as a result. The overall effect is an increase in the filtration fraction, which is calculated as GFR divided by RPF.

Changes in plasma protein levels can have significant effects on renal function. Increased plasma protein levels lead to a decrease in GFR due to an increase in glomerular capillary oncotic pressure (πGC). However, there is no change in RPF. The filtration fraction decreases as a result of the reduced GFR in relation to the unchanged RPF.

The presence of a ureteral stone, which causes an obstruction, results in a decrease in GFR due to an increase in Bowman space hydrostatic pressure (PBS). However, RPF remains unchanged. This obstruction leads to a decrease in the filtration fraction as a result of the reduced GFR with an unchanged RPF.

OpenStax. (2022). Anatomy and Physiology 2e. Rice University. Retrieved June 15, 2023. ISBN-13: 978-1-711494-06-7 (Hardcover) ISBN-13: 978-1-711494-05-0 (Paperback) ISBN-13: 978-1-951693-42-8 (Digital). License: Attribution 4.0 International (CC BY 4.0). Access for free at openstax.org.

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Script:
  1. Clearance equation is crucial for determining the efficiency of renal clearance by comparing urine and plasma concentrations of a substance.
  2. It is widely used in clinical settings to assess renal function, drug clearance, and estimate glomerular filtration rate (or GFR), providing valuable insights into kidney condition.
  3. Renal blood flow (or RBF) is regulated by vasoconstrictor and vasodilator mechanisms, ensuring adequate perfusion despite changes in arterial pressure.
  4. RPF is measured using para-aminohippuric acid clearance, with RBF derived from RPF adjusted for hematocrit, both critical for assessing renal function and hemodynamics.
  5. GFR can be estimated using inulin clearance, but more commonly through serum creatinine and blood urea nitrogen levels.
  6. GFR tends to decrease with age, emphasizing the importance of monitoring renal function in elderly patients, even if serum creatinine levels remain relatively stable.
  7. Filtration fraction, calculated as GFR divided by RPF, represents the proportion of plasma flow filtered in glomerular capillaries.
  8. It influences renal reabsorption and peritubular capillary protein concentration.
  9. Changes in arteriolar constriction, whether afferent or efferent, have profound effects on GFR and renal function, mediated by various physiological mechanisms.
  10. Understanding how factors like plasma protein levels and obstructive conditions affect GFR, RPF, and filtration fraction is crucial for diagnosing and managing renal disorders effectively.
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