Elements of renal function (berne Ch. 32) Flashcards
The pH is maintained by buffers within the body fluids and by the coordinated action of what organs
Lungs, liver, and kidneys
The kidneys excrete a number of the end products of metabolism. These waste products include…
Amino acids:
Nucleic acids:
Muscle creatine
Amino acids: Urea
Nucleic acids: Uric acid
Muscle creatine: creatinine
The kidneys regulate (3)
- Body fluid osmolality and volumes
- Electrolyte balance
- Acid-base balance
* * In addition, the kidneys excrete metabolic products and foreign substances and produce and secrete hormones
Kidneys are important endocrine organs that produce (3)
Renin, calcitriol, and erythropoietin
Renin-angiotensin-aldosterone system helps regulate what? (2)
Blood pressure and Na and K balance
In patients with renal disease, the kidneys’ ability to produce calcitriol is impaired, and levels of this hormone are reduced. What is the result of calcitriol reduction?
Ca absorption by the intestine is decreased
**This reduced intestinal Ca absorption contributes to the bone formation abnormalities seen in patients with chronic renal disease
True or false
Chronic renal failure may also manifest anemia
True
** Another consequence of many kidney diseases is a reduction in erythropoietin production and secretion. Erythropoietin stimulates red blood cell formation by the bone marrow
Patients in whom the glomerular filtration rate (GFR) is less than 10% of normal are said to have _____
End-stage renal disease (ESRD)
The medial side of each kidney contains an indentation. What structures pass through this indentation?
Renal artery and vein, nerves, and pelvis
The medulla in the human kidney is divided into conical masses called ____
Renal pyramids
The base of each renal pyramid originates at what structure?
Corticomedullary border
The apex each renal pyramid terminates in what structure?
Papilla – lies within a minor calyx (collect urine from each papilla)
Numerous minor calyces expand into two or three open-ended pouches called _____
Major calyces
** The major calyces in turn feed into the pelvis
Blood flow to the two kidneys is equivalent to about what percent of the cardiac output in resting individuals?
25% (1.25 L/min)
Renal artery branches progressively to form what structures? (4)
Interlobar artery, the arcuate artery, the interlobular artery, and the AFFERENT arteriole
The nephron consists of a what structures (4)
renal corpuscle, proximal tubule, loop of Henle, distal tubule
It is composed of the straight part of the proximal tubule, the descending thin limb (which ends in a hairpin turn), the ascending thin limb and the thick ascending limb
Loop of Henle
** Ascending thin limb – present in nephrons with long loop of Henle
The renal corpuscle consists of what structures? (2)
Glomerular capillaries and Bowman’s capsule
Near the end of the thick ascending limb, the nephron passes between the afferent and efferent arterioles of the same nephron. This short segment of the thick ascending limb is called ____
Macula densa
The distal tubule begins a short distance beyond the macula densa and extends to the point in the cortex where two or more nephrons join to form what structure?
Cortical collecting duct
Brush border is present only in (a) proximal tubule (b) distal tubule
a. Proximal tubule
True or false
In proximal tubule cells, apical membrane is highly invaginated. These invaginations contain many mitochondria
False – basolateral membrane
- Proximal tubule cells have an extensively amplified apical membrane (the urine side of the cell) called brush border
- In contrast, the descending and ascending thin limbs of Henle’s loop have poorly developed apical and basolateral surfaces and few mitochondria
The collecting duct is composed of two cell types:
Principal cells and intercalated cells
This cell type of collecting duct has a moderately invaginated basolateral membrane and contains few mitochondria and plays an important role in reabsorption of NaCl
Prinicipal cells
This cell type of collecting duct plays an important role in the regulation of acid-base balance and has many mitochondria
Intercalated cells
All cells in the nephron, except _____, have in their apical plasma membrane a single nonmotile primary cilium that protrudes into the tubule fluid
Intercalated cells
**Primary cilia are mechanosensors and
chemosensors and they initiate Ca- dependent signaling pathways, including those that control kidney cell function, proliferation, differentiation, and apoptosis
Expressed in the membrane of primary cilia and mediate entry of Ca into cells
Polycystin 1 (encoded by the PKD1 gene) and polycystin 2 (encoded by the PKD2 gene) **PKD1 and PKD2 are thought to play an important role in flow-dependent K secretion by principal cells of the collecting duct.
Afferenet arteriole leads into _____; efferent arteriole leads into _____
Glomerolus; peritubular capillaries
**The glomerulus consists of a network of capillaries supplied by the afferent arteriole and drained by the efferent arteriole
When compared with superficial nephrons, juxtamedullary nephrons differ anatomically in two important ways:
- The loop of Henle is longer and extends deeper into the medulla
- The efferent arteriole forms not only a network of peritubular capillaries but also a series of vascular loops called the vasa recta
The vasa recta descend into the medulla, where they form capillary networks that surround what structures?
Collecting ducts and ascending limbs of the loop of Henle
Passive movement of an essentially protein-free fluid from the glomerular capillaries into Bowman’s space
Ultrafiltration
**First step of urine formation
Forms the visceral layer of Bowman’s capsule
Podocytes – epithelial cells that cover the capillaries
Structures making up the filtration barrier
The capillary endothelium, basement membrane, and foot processes of podocytes
This part of the glomerolus function primarily as a charge-selective filter
Glomerular basement membrane
Anatomy of podocyte foot processes
Organizes nephrin and NEPH1 in specific microdomains in the plasma membrane, which is important for signaling events that determine the structural integrity of podocyte foot processes
Podocin
This complex structure function primarily as a size-selective filter
Filtarion-slit
** The processes of the podocytes interdigitate to cover the basement membrane and are separated by apparent gaps called filtration slits. Each filtration slit is bridged by a thin diaphragm
The filtration slit diaphragm, which appears as a continuous structure when viewed by electron microscopy, is composed of several proteins:
nephrin (NPHS1), NEPH-1, podocin (NPHS2), a-actinin 4 (ACTN4) and CD2-AP
These cells possess many properties of smooth muscle cells which surround the glomerular capillaries and provide structural support for the glomerular capillaries secrete the extracellular matrix, exhibit phagocytic activity by removing macromolecules from the mesangium, and secrete prostaglandins and proinflammatory cytokines
Mesangial cells
IN THE CLINIC
Characterized by an increase in permeability of the glomerular capillaries to proteins and by loss of normal podocyte structure, including effacement (i.e., thinning) of the foot processes
Nephrotic syndrome
- *The augmented permeability to proteins results in an increase in urinary protein excretion (proteinuria). Thus, the appearance of proteins in urine can indicate kidney disease. Hypoalbuminemia often develops in individuals with this syndrome as a result of the proteinuria
- Generalized edema is commonly seen in individuals with nephrotic syndrome
Nephrins from opposite foot processes interdigitate in the center of the slit. In the slit, nephrin interacts with what proteins?
NEPH1 and NEPH2, FAT1 and FAT2 and P-cadherin
IN THE CLINIC
Characterized by hematuria (i.e.,blood in urine) and progressive glomerulonephritis
(i.e., infl ammation of the glomerular capillaries) and accounts for 1% to 2% of all cases of ESRD
Alport’s syndrome
IN THE CLINIC
Alport’s syndrome is caused by defect in ____
Type IV collagen (encoded by the COL4A5 gene), a major component ofthe glomerular basement membrane
Structures that make up the juxtaglomerular apparatus include the following: (3)
- The macula densa of the thick ascending limb
- Extraglomerular mesangial cells
- Renin- and angiotensin II–producing granular cells of the afferent arteriole
The nerve supply to the kidneys consists of sympathetic nerve fibers that originate in what plexus?
Celiac plexus
** There are no parasympathetic innervations
Adrenergic fibers that innervate the kidneys release norepinephrine and dopamine. The adrenergic fibers lie adjacent to what structure?
Smooth muscle cells of the major branches of the renal artery (interlobar, arcuate, and interlobular arteries) and the afferent and efferent arterioles
The coordinated actions of the nephron’s various segments determine the amount of a substance that appears in urine. This represents three general processes:
- Glomerular filtration
- Reabsorption of substance from tubular fluid back into blood
- Secretion of substance from blood to tubule fluid
Based on the Fick principle (i.e., mass balance or conservation of mass)
Renal clearance
Mass balance relationship of a kidney
Input:
Output:
Input: Renal artery: Pax X RPFa
Output: Renal vein + ureter: (Pvx X RPFv) + (Ux X V)
** Pax and Pvx are the concentrations of substance x in the renal artery and renal vein plasma, respectively
** RPFa and RPFv are renal plasma flow rates in the artery and vein, respectively
**Ux is the concentration of substance x in urine
**V is the urine flow rate
The principle of renal clearance emphasizes what function of the kidney?
Excretory function of the kidneys
**it considers only the rate at which a substance is excreted into urine and not its rate of return to the systemic circulation in the renal vein
In terms of mass balance, the urinary excretion rate of substance x (Ux X V) is proportional to _____
Plasma concentration of substance x (Pax)
Pax X Cx is equal to _____
Ux X V
**Cx is the rate at which substance x is removed from plasma by the kidneys (RENAL CLEARANCE)
Sum of the filtration rates of all functioning nephrons
Glomerular filtration rate (GFR)
Renal handling of creatinine
Amount filtered:
Amount excreted:
Amount filtered: PCr X GFR
Amount excreted: UCr X V
**Amount filtered is equal to amount excreted
IN THE CLINIC
Used to estimate the GFR in clinical practice. It is synthesized at a relatively constant rate, and the amount produced is proportional to the muscle mass
Clearance of Creatinine
** Because measurements of GFR are cumbersome, kidney function is usually assessed in the clinical setting by measuring PCr, which is inversely related to GFR
GFR
(UCr X V)/PCr
- *UCr = urine concentration of creatinine
- *PCr = plasma concentration of creatinine
Renal clearance (Cx)
(Ux X V)/Px
- *Ux = urine concentration of substance x
- *Px = plasma concnetration of substance x
Any substance that meets these following criteria can serve as an appropriate marker for the measurement of GFR
- Be freely filtered across the glomerulus into Bowman’s space
- Not be reabsorbed or secreted by the nephron
- Not be metabolized or produced by the kidney
- Not alter the GFR
The portion of filtered plasma
Filtration fraction
Filtration Fraction
GFR divided by RPF
**Under normal conditions the filtration fraction averages 0.15 to 0.20, which means that only 15% to 20% of the plasma that enters the glomerulus is actually filtered. The remaining 80% to 85% continues on through the glomerular capillaries and into the efferent arterioles and peritubular capillaries. It is finally returned to the systemic circulation in the renal vein
In normal adults, the GFR ranges from
Male: 90 to 140 mL/min
Female: 80 to 125 mL/min
IN THE CLINIC
Reduction of the negative charges on the glomerular wall results in the filtration of proteins based on ______
Size only
- *In this situation the relative filterability of proteins depends only on the molecular radius. Accordingly, excretion of polyanionic proteins (20 to 42 A) in urine increases because more proteins of this size are filtered
- *In a number of glomerular diseases the negative charges on the filtration barrier are reduced because of immunological damage and inflammation. As a result, the filtration of proteins is increased, and proteins appear in urine (proteinuria).
The glomerular filtration barrier determines the composition of the plasma ultrafiltrate. It restricts the filtration of molecules on the basis what properties?
Size and electrical charge
Force that promote the movement of fluid from the glomerular capillary into Bowman’s space
The hydrostatic pressure in the glomerular capillary (PGC)
- *PGC is the only force that favors filtration because oncotic pressure in Bowman’s space (πBS) is near zero
- *The hydrostatic pressure in Bowman’s space (PBS) and the oncotic pressure in the glomerular capillary (πGC) oppose filtration
A net ultrafiltration pressure (PUF) of 17 mm Hg exists at what end of the glomerolus?
Afferent
- *whereas at the efferent end it is 8 mm Hg
- *PUF = PGC - PBS - πGC
True or false
PGC decreases slightly along the length of the capillary
True - because of the resistance to flow along the length of the capillary
True or false
πGC decreases slightly along the length of the capillary
False
**πGC increases along the length of the glomerular capillary because water is filtered and protein is retained in the glomerular capillary, the protein concentration in the capillary rises, and πGC increases
Blood flow through any organ may be represented by what equation?
Q = ∆P/R
- *Q = blood flow
- *∆P = mean arterial pressure minus venous pressure for that organ
- *R = resistance to flow through that organ
PGC is affected in three ways:
- Changes in afferent arteriolar resistance:
- Changes in efferent arteriolar resistance:
- Changes in renal arteriolar pressure:
- Changes in afferent arteriolar resistance: A decrease in resistance increases PGC and GFR, whereas an increase in resistance decreases them
- Changes in efferent arteriolar resistance: A decrease in resistance reduces PGC and GFR, whereas an increase in resistance elevates them
- Changes in renal arteriolar pressure: An increase in blood pressure transiently increases PGC (which enhances GFR), whereas a decrease in blood pressure transiently decreases PGC (which reduces GFR)
IN THE CLINIC
A reduction in the GFR in disease states is most often due to decreases in Kf because of the loss of filtration surface area. The GFR also changes in pathophysiological conditions because of changes in PGC, πGC, and PBS.
Changes in Kf:
Changes in Kf: Increased Kf enhances the GFR, whereas decreased Kf reduces the GFR. Some kidney diseases reduce Kf by decreasing the number of filtering glomeruli (i.e., diminished surface area). Some drugs and hormones that dilate the glomerular arterioles also increase Kf. Similarly, drugs and hormones that constrict the glomerular arterioles also decrease Kf.
**filtration fraction
IN THE CLINIC
A reduction in the GFR in disease states is most often due to decreases in Kf because of the loss of filtration surface area. The GFR also changes in pathophysiological conditions because of changes in PGC, πGC, and PBS.
Changes in PGC:
Changes in PGC: With decreased renal perfusion, the GFR declines because PGC falls. A reduction in PGC is caused by a decline in renal arterial pressure, an increase in afferent arteriolar resistance, or a decrease in efferent arteriolar resistance.
IN THE CLINIC
A reduction in the GFR in disease states is most often due to decreases in Kf because of the loss of filtration surface area. The GFR also changes in pathophysiological conditions because of changes in PGC, πGC, and PBS.
Changes in πGC:
Changes in πGC: An inverse relationship exists between πGC and GFR. Alterations in πGC result from changes in protein synthesis outside the kidneys. In addition, the protein loss in urine caused by some renal diseases can lead to a decrease in the plasma protein concentration and thus in πGC.
IN THE CLINIC
A reduction in the GFR in disease states is most often due to decreases in Kf because of the loss of filtration surface area. The GFR also changes in pathophysiological conditions because of changes in PGC, πGC, and PBS.
Changes in PBS:
Changes in PBS: Increased PBS reduces the GFR, whereas decreased PBS enhances the GFR. Acute obstruction of the urinary tract (e.g., a kidney stone occluding the ureter) increases PBS.
RBF
(Aortic pressure-venous pressure)/(Renal vascular resistance)
The phenomenon whereby RBF and GFR are maintained relatively constant
Autoregulation
Two mechanisms are responsible for the autoregulation of RBF and GFR:
One mechanism that responds to changes in arterial pressure and another that responds to changes in [NaCl] in tubular fluid
**Both regulate the tone of the afferent arteriole
Two mechanisms are responsible for the autoregulation of RBF and GFR
Myogenic mechanism:
tubuloglomerular feedback:
Myogenic mechanism: Related to an intrinsic property of vascular smooth muscle - the tendency to contract when stretched. When arterial pressure rises and the renal afferent arteriole is stretched, the smooth muscle contracts. Because the increase in resistance of the arteriole offsets the increase in pressure, RBF and therefore GFR remain constant
Tubuloglomerular feedback: NaCl-dependent mechanism that involves a feedback loop in which the concentration of NaCl in tubular fluid is sensed by the macula densa of the juxtaglomerular apparatus and converted into a signal or signals that affect afferent arteriolar resistance and thus the GFR
Cellular mechanism whereby an increase in the delivery of NaCl to the macula densa causes vasoconstriction of the afferent arteriole of the same nephron
Tubuloglomerular feedback
- An increase in GFR elevates [NaCl] in tubule fluid at the macula densa. This in turn enhances uptake of NaCl across the apical cell membrane of macula densa cells via the 1Na-1K2Cl (NKCC2) symporter, which leads to an increase in [ATP] and [adenosine] (ADO).
- ATP binds to P2X receptors and adenosine binds to adenosine A1 receptors in the plasma membrane of smooth muscle cells surrounding the afferent arteriole, both of which increase intracellular [Ca]. The rise in [Ca] induces vasoconstriction of the afferent arteriole, thereby returning GFR to normal levels
True or false
Autoregulation occurs at any arterial pressure.
False - Autoregulation is absent when arterial pressure is less than 90 mm Hg
Major Hormones That Influence the Glomerular Filtration Rate and Renal Blood Flow
Vasoconstrictors:
Sympathetic nerves
Angiotensin II
Endothelin
Major Hormones That Influence the Glomerular Filtration Rate and Renal Blood Flow
Vasodilators:
Prostaglandins (PGE1, PGE2, PGI2)
Nitric oxide (NO)
Bradykinin
Natriuretic peptides (ANP, BNP)
The afferent and efferent arterioles are innervated by sympathetic neurons; however, sympathetic tone is minimal when the volume of extracellular fluid is (a) normal (b) increased (c) decreased
a. Normal
Norepinephrine and dopamine is to sympathetic nerves; epinephrine is to _____
Adrenal medulla
** Norepinephrine and epinephrine cause vasoconstriction by binding to a1-adrenoceptors, which are located mainly on the afferent arterioles
Angiotensin II is produced by ____
Kidney
** The efferent arteriole is more sensitive to angiotensin II than the afferent arteriole. Therefore, with low concentrations of angiotensin II, constriction of the efferent arteriole predominates, and GFR increases and RBF decreases. However, with high concentrations of angiotensin II, constriction of both afferent and efferent arterioles occurs, and GFR and RBF both decrease
A catecholamine-metabolizing hormone produced by the kidneys, facilitates the degradation of catecholamines
Renalase
True or false
Prostaglandins play a major role in regulating RBF in healthy, resting people
False
**Prostaglandins do not play a major role in regulating RBF in healthy, resting people. However, during pathophysiological conditions such as hemorrhage, prostaglandins (PGI2, PGE1, and PGE2) are produced locally within the kidneys, and they increase RBF without changing GFR
Synthesis of prostaglandins: dehydration and stress (e.g., surgery, anesthesia), angiotensin II, and sympathetic nerves; Inhibition of prostaglandins: ________
Nonsteroidal antiinflammatory drugs (NSAIDs), such as aspirin and ibuprofen
True or false
NO is an endothelium-derived relaxing factor, is an important vasodilator under basal conditions, and it counteracts the vasoconstriction produced by angiotensin II and catecholamines
True
- When blood flow increases, greater shear force acts on endothelial cells in the arterioles and increases the production of NO
- Increased production of NO causes dilation of the AFFERENT and EFFERENT arterioles
A potent vasoconstrictor secreted by endothelial cells of the renal vessels, mesangial cells, and distal tubular cells in response to angiotensin II, bradykinin, epinephrine, and endothelial shear stress
Endothelin
** Production of endothelin is elevated in a number of glomerular disease states (e.g., renal disease associated with diabetes mellitus)
Secretion of atrial natriuretic peptide (ANP) by the _____; brain natriuretic peptide (BNP) by the _____
Cardiac atria; cardiac ventricle
- increases when extracellular fluid volume is expanded
- Both ANP and BNP dilate the afferent arteriole and constrict the efferent arteriole. Therefore, ANP and BNP produce a modest increase in GFR with little change in RBF
True or false
The local release of histamine modulates RBF during inflammation and injury only
False
- The local release of histamine modulates RBF during the resting state and during inflammation and injury
- Histamine decreases the resistance of the afferent and efferent arterioles and thereby increases RBF without elevating GFR
Dopamine is produced in the (a) proximal tubule (b) distal tubule
a. Proximal tubule
* * Dopamine has several actions within the kidney, such as increasing RBF and inhibiting rennin secretion
NO production is stimulated by ____
Shear stress, acetylcholine, histamine, bradykinin, and ATP
