Glomerular Filtration Flashcards
Describe the. Urinary system
Bean-shaped organs, located just under the rib cage behind the peritoneal cavity, close to the posterior abdominal wall, one each side of the vertebral column
- Approximately three vertebrae in length (T12 to L3). Adrenal glands sits immediately superior to the kidneys
- The rounded, outer convex surface of each kidney faces the side of the kidney faces the side of the body, and the indented surface, called the hilum, faces the spine.
- Renal colic is pain in the flank that radiates toward the groin. It is usually severe and most commonly caused by renal canaculi (kidney stones)
What are the major structural differences of the kidney?
The kidney has outer cortex and an inner medulla. Urine leaving the nephrons —> renal pelvis —> ureter —> bladder
Where May kidney stones cause pain/obstruction?
Kidney stones may cause pain by obstruction at the
-junction of renal pelvis and ureter
- At the site where the ureter passes over the pelvic brim
- At the junction between the ureter and bladder
Contrast: cortex vs medulla osmolarity difference
- Osmolarity of cortex= plasma, but the osmolarity of the inner medulla is increased several fold
- The osmotic gradient is used to recover all of the water that is filtered from the vasculature each day (average urinary water excretion is 1-2 L/d)
What are the functions of kidneys?
Endocrine-
Production of hormones
Erythropoietin-stimulates bone marrow for the production of red blood cells
Renin- converts angiotensinogen to angiotensin I
Hydroxylase 25-OH to 1,25-OH vitamin D
Homeostasis
-regulation of extracellular fluid volume and blood pressure
- Regulation of osmolarity
- Maintenance of ion balance
- Homeostatic regulation of pH
- Excretion of wastes
Note: the cysts form within the nephron and progressively enlarge and compress the surrounding tissues, preventing fluid flow through tubules
What are the types of nephrons and tubular segments?
Two types of nephron: (85%) cortical and Juxtaglomerular (15%) nephron
Nephron structures in the
- Cortex—> consists of oroximal and distal convuluted tubules as well as the initial segments of the collecting duct
- Medulla—> consists of the long loops of Henle and the terminal regions of the collecting duct
Juxtamedullary nephrons are important for urine concentration
What is a nephron?
The functional unit of the kidney consisting glomerulus and renal tubule
What is the glomerulus?
A capillary network and is surrounded by Bowman’s capsule (or Bowman’s space), which is continuous with the first tubule of the nephron
What are the renal tubules comprised of?
- PCT
- Loop of Henle (proximal straight tubule, thin descending limb, thick ascending & distal straight tubule)
- Distal convuluted tubule
Outline the blood supply to the kidney
Renal artery—> segmental artery—> interlobar artery—> arcuate artery—> interlobular artery- -> afferent arteriole—> glomerulus—> efferent arteriole—> peritubular capillaries—> interlobular vein—> arcuate vein —> interlobular vein—> segmental vein —>. Renal vein
Outline blood supply of the glomerulus
Afferent arteriole—>Glomerular capillaries (filtration here although not all blood filtered at each pass)—> efferent arteriole—> peritubular capillaries (wraps around both the proximal and distal tubules
Describe blood supply of proteins the nephron
Cortical nephrons are surrounded by peritubular capillary network and the interstitium is close to an isotonic environment
Vasta recta—> specialized peritubular capillaries close to juxtamedullary nephrons ONLY
Low blood flow in the renal medulla preserve the medullary hypertonicity necessary for the concentration of urine but causes it to be susceptible to ischemia in the setting of hypotension or renal vasoconstriction
The slow flow also keeps the pO2 of the medulla lower than that in the cortex. A sustained decrease in renal perfusion may result in acute renal failure (ARF)
What do macula densa cells do?
Sense distal Tubule flow and release paracrines that affect afferent arteriole diameter
Summarize the anatomy of the glomerulus
Renal corpuscle —> Glomerulus and the Bowman’s capsule
Juxtaglomerular apparatus
- macula densa cells: specialized chemoreceptors cells in the walls of the distal convoluted tubule, which respond to changes in solute concentration (especially Na)
- Juxtaglomerular cells may modified smooth muscle cells located in the walls of the afferent arteriole
- Mesangial cells
What are the elements of Glomerular filtration barrier?
Ultrafiltration of blood across the Glomerular capillaries into Bowman’s space is the first step in urine formation
- Endothelial fenestration of the Glomerular capillaries-Numerous > 70-90 (Nm or A)
- Glomerular basement membrane
- Fused basal lamina of the endothelial cells and podocytes
- Heparan sulphate repels negatively charged molecules
- Podocytes layer (visceral layer of the Bowman’s capsule)
- Modified epithelial called podocytes, highly reminded. Primary processes—> secondary processes—> tertiary processes processes (pedicels)
- filtration slits between pedicels (about 40 nm or A)
- Modified epithelial called podocytes, highly reminded. Primary processes—> secondary processes—> tertiary processes processes (pedicels)
What are the main properties of the Glomerular filtration barrier?
-Filterability of solutes is inversely related to their size
A filterability of 1 means the substance is filtered as freely as water, whereas filterability of 0.75 means the substance is filtered only 75% as rapidly as water
-As molecular weight of the molecule approaches that of albumin, the filterability approaches zero
Albumin is about 6 Nn whereas the pores of the Glomerular membrane are about 8 nm. WHY NOT FILTER?
It posses a negative charge and the electrostatic repulsion exerted by negative charges on the Glomerular capillary wall proteoglycans
Negatively charged large molecules are filtered less easily than positive,y charged molecules of equal molecular size
What does a Glomerular capillary do?
Keeps protein molecules in the blood
In minimal change disease, protein molecules spill into the urine because of abnormalities in the capillary wall
By electron microscopy, a normal Glomerular capillary has separate foot processes
A minimal change disease Glomerular capillary has fused foot processes
What is Glomerular filtration rate?
This is the net fluid flow across the capillary wall. Normal GFR value for both kidneys is about 125 ml/min
What are the influences of GFR?
Filtration coefficient (Kf)
- Surface area of Glomerular capillaries available for filtration
- Permeability of interface between the capillary and Bowman’s capsule
Net filtration pressure (🔼P)
(Hydrostatic pressure- oncotic pressure- Bowman’s fluid pressure)
Renal insufficiency occurs when GFR is low. A progressive decline in GFR indicates the stages of chronic kidney disease
Kf- Glomerular capillary filtration coefficient
🔼P- Net filtration pressure
What drives GFR?
PGC= hydrostatic pressure in Glomerular capillaries
What are the factors of the net filtration pressure?
Starlings forces(pressures):
Hydrostatic (P)—> push water
Oncotic (pi)—> pull water
-pi is influenced by the presence of protein, specifically albumin
Forces favoring filtration
- Hydrostatic Glomerular capillary (PGC= 60mmHg)
- Oncotic Bowman’s space= (piBS= 0 mmHg)
Fo4ces favoring Reabsorption
- Hydrostatic Bowman’s space (PBS= 18mmHg)
- Oncotic Glomerular capillary(PiGC= 32 mmHg )
What does Kf measure?
Measure of the product of hydraulic conductivity and surface area of the Glomerular capillaaries
What is the impact of increased and decreased Kf?
Increased Kf raises GFR and decreased Kf reduces GFR, however changes in Kf probably do not provide a primary mechanism for the normal day to day regulation of GFR
Diseases (Chromic, uncontrolled hypertension and diabetes mellitus) lowers Kf by reducing the number of functional Glomerular capillaries (thereby reducing the surface area for filtration) or by increasing the thickness of the Glomerular capillary membrane (reducing hydraulic conductivity)
Mesangial cells contraction—> reduce capillary surface area (Kf) —> reduce GFR. The role of mesangial cells is minor compared with that of Glomerular arterioles
Contrast nephrotic and nephritis syndrome
Nephrotic syndrome is a kidney disorder that causes your body to excrete too much protein in your urine. In addition, Nephritic Syndrome increases RBC releases into the urine as hematuria
Oncotic pressure in the Bowman’s space increases and thus, favors filtration
Clinical: Peripheral edema, proteinuria, hyperlipidemia, hypoalbunemia
What is urinary cholithiasis?
- Kidney stones causing obstruction and dilation of urinary system
- Indrease in hydrostatic pressure within the bowman space thus, opposes filtration
This situation reduces GFR and eventually can cause hydronephrosis (distention and dilation of the renal pelvis and calyces) and can damage or even destroy the kidney unless the obstruction is relieved
What causes changes in starling forces?
Sterling forces change as blood passes along the Glomerular capillary from the afferent arteriole and to the efferent arteriole
Q. Significance in peritubular capillary dynamics?
ANS: increased oncotic pressure in peritubular capillary increases absorption
Q. Why Glomerular oncotic pressure increases as blood passes from the afferent arteriole through the Glomerular capillaries to the efferent arteriole?
ANS: due to the filtration fraction (FF)
1/5(20%) of the fluid (plasma) in the capillaries filters into the Bowman’s capsule, thereby concentrating the Glomerular plasma proteins (by 20%) that are not filtered
What is the formula for filtration fraction?
Filtration fraction= GFR/renal plasma flow
How can we know if Reabsorption in peritubular capillaries occurs?
Calculate net Reabsorption pressure
What 8s filtration fraction?
Represents the loss of protein-free fluid into the Bowman’s, thereby increasing the concentration of protein in the plasma
FF= GFR/RPF=
GFR=125mL/min and RPF=625ml/min
FF=125/625=0.2
What does filtration fraction affect?
FF affects oncotic pressure in the peritubular capillaries (pic)
The greater the FF, the higher the oncotic pressure in the peritubular capillaries. If FF decreases, then piPC decreases
piC is the driving force for Reabsorption
What are the general rules of renal hemodynamics?
Vasoconstriction
- Flow decreases
- Pressure upstream increases
- Pressure downstream decreases
Vasodilation
- Flow increases
- Pressure gradient upstream decreases
- Pressure downstream increases
What are the consequences of afferent arteriole vasoconstriction?
- Decrease of hydrostatic pressure of Glomerular capillaries
- Decrease in hydrostatic pressure 9f peritubular capillaries
- Decrease in renal plasma/blood volume
What is the effect of afferent arteriole vasodilation (PGE, PGI2 and Bradykinin)?
- Increase in hydrostatic pressure of Glomerular capillaries
- Increase in hydrostatic pressure of peritubular capillaries
- Increase in renal plasma/blood flow
PPC=hydrostatic pressure of peritubular capillary
PGC= hydrostatic pressure of Glomerular capillary
What are the effects in efferent arteriole vasoconstriction?
- Increase in hydrostatic pressure of Glomerular
- Decrease in hydrostatic pressure of peritubular capillaries
- Decrease in renal plasma/blood flow
What are the effects of efferent arteriole vasodilation?
- Decrease in hydrostatic pressure of Glomerular capillaries
- Increase in hydrostatic pressure of peritubular capillaries
- Increase in renal plasma/blood flow
How does autoregulation in kidneys maintain a constant GFR?
Autoregulation in the kidneys maintains a relatively constant GFR and allows precise control of renal excretion of water and solutes
-If GFR—> needed substances cannot be reabsorbed quickly enough and is lost in the urine
- If GFR too low—> too much Reabsorption occurs inclusive of waste products such as Urea
- RBF remains relatively stable over a mean arterial pressure (MAP) range of about 80 to 180mmHg
How does autoregulation of afferent arteriole affect resistance?
Autoregulation is primarily accomplished due to changes in the resistance of the afferent arterioles by two mechanisms:
- Myogenic mechanisms —> the intrinsic property of smooth muscle is to contract when stretched
- Tubuloglomerular feedback (TGF):
- TGF is an autoregulation mechanism mediated by the juxtaglomerular apparatus (JGA) that adjusts RBF and GFR to optimize fluid flow through the renal tubule
When happens when GFR increases?
Increased GFR —> increased tubule flow—> increased NaCl(macula densa)—> depolarization (macula densa) this on one hand increases adenosine, causing afferent arteriole constriction and efferent arteriole dilation
This causes a decrease in PUF, GFR and thus, tubule flow decreases
Depolarization of macula densa also leads to Ca2+ influx into macula densa
This then leads to decreased renin release (AA granular cells) preventing formation of angiotensin II
What happens when decreased GFR?
Decrease GFR—> decreased tubule flow—> decreased NaCl (macula densa)—> depolarization (macula densa ) (decreased adenosine) —> decreased Ca2+ influx (macula densa)—> renin release increased (afferent arteriole granule cells)—> angiotensin II —> efferent arteriole constriction —> increased PUF, increasedGFR lead to increased tubule flow
PUF = capillary hydrostatic ultrafiltration pressure
