What are the functions of the kidneys?
- Regulation of ECF and BP
- Regulation of osmolarity
- Ion balance
- pH regulation
- Excretion
- Production of hormones
What are the functional units of the kidney?
The nephron is the functional unit of the kidney.
The nephron comprised of 2 functional units:
- Renal Corpuscle
- Renal Tubule
What is the renal corpuscle comprised of?
Glomerulus- capillary network
Glomerular(Bowman’s) capsule- double walled cup surrounding glomerulus
What is the renal tubule comprised of?
- proximal convoluted tubule
- Loop of Henle divided into descending and ascending limbs with thin and thick segments
- distal convoluted tubules
What is the function of renal corpuscle?
Filters blood plasma
What is the function of the renal tubule?
Filtered fluid passes into the proximal convoluted tubule
What is the purpose of fenestration of glomerular endothelial cells in the filtration membrane?
Fenestrations/pores of glomerular endothelial cell prevents filtration of blood cells but allows all components of blood plasma to get pass through
What is the purpose of the basal lamina in the glomerulus?
Prevents filtration of larger proteins
What is the function of the slit membrane between pedicels?
Prevents filtration of medium-sized proteins
Describe the flow of fluid through the juxtamedullary nephron
Glomerular (Bowman’s) capsule -> Proximal convoluted tubule ->
descending limb of the nephron loop -> Thin ascending limb of the nephron ->
thick ascending limb of the nephron loop -> Distal convoluted tubule(drains into the collecting duct)
Describe the flow of fluid through a cortical nephron
- Glomerular (Bowman’s) Capsule
- Proximal Convoluted tubule
- Descending limb of the nephron loop
- Ascending limb of the nephron loop
- Distal convoluted tubule(drains into collecting duct)
Describe the layers of glomerular capsule
Consists of visceral and parietal layers
Visceral layer consists of modified simple squamous epithelial cells called podocytes
Parietal layer of the glomerular capsule consists of simple squamous epithelium and forms the outer wall of the capsule
What happens to the fluid filtered from the glomerular capillaries ?
Fluid enters the capsular space between the two layers of the glomerular capsule, which is continuous with the lumen of the renal tubule
What types of cells make up the proximal convoluted tubule?
Cells are simple cuboidal epithelial cells with a prominent brush border of microvilli on their apical surface(surface facing the lumen)
What is the cell type of the descending limb of the nephron loop?
Composed of simple squamous epithelium (same as the thin ascending limb( first part) of the ascending limb)
What types of cells make up the thin ascending limb(first part of the ascending limb)?
Simple squamous epithelium
What types of cells make up the thick ascending limb of the nephron loop?
Composed of simple cuboidal to low columnar epithelium
What types of cells make up the last part of the distal convoluted tubules and continuing into the collecting duct?
- Most of the cells are principal cells
- intercalated cells
Where are the intercalated cells and what is their purpose?
Located in distal convoluted tubules and play a role in the homeostasis of blood pH.
Where are the principal cells located and what is their purpose?
Located in the distal convoluted tubules and have receptors for both ADH and aldosterone , two hormones that regulate kidney functions
Contrast the cells that make up the first and last parts of the distal convoluted tubules and collecting duct
Most of the distal convoluted is made up of simple cuboidal epithelial cells
Last part of distal convoluted tubule and collecting duct- simple cuboidal epithelium consisting of principal cells and intercalated cells
What does the Juxtaglomerular Apparatus consist of?
Macula densa
Juxtaglomerular cells
What is the function of the Juxtaglomerular apparatus ?
Helps regulate blood pressure in the kidneys
What is the Macula densa?
An area of closely packed specialized cells lining the wall of the distal tubule where the DCT meets the thick ascending limb of the nephron loop
What are the juxtaglomerular cells?
Modified smooth muscle fibers found in the walls of Afferent and efferent arterioles
State the 3 basic functions of the nephron
- Glomerular filtration
- Tubular Reabsorption
- Tubular Secretion
Describe glomerular filtration
The first step of urine production, water and most solutes in are filtered and move into the glomerular capsule
Describe tubular reabsorption
Renal tubules and collecting ducts reabsorb about 99% of the filtered water and many solutes from filtered fluid
Describe tubular secretion
Renal tubules cells of collecting ducts release secretions such as wastes, drugs and excess materials as filtered fluid flows through
What are the 3 barriers of the the filtration membrane ?
- Glomerular endothelial fenestrations
- Basal lamina between endothelium and podocytes
- Pedicels of podocytes create filtration slits
What are the functions of the filtration membrane?
Prevents filtration of water and small solutes
Prevents filtration of most plasma proteins, blood cells and platelets
Why is the volume of filtered fluid so large?
- Large surface area
- thin and porous filtration membrane
- Hugh glomerular capillary blood pressure
Define glomerular filtration rate
The amount of filtrate formed in all renal corpuscles of both kidneys each minute
What is the average Glomerular Filtration Rate I’m adults?
Males- 125 mL/min
Females- 150 mL/min
What 3 mechanisms regulate GFR?
- Renal autoregulation
- Neural regulation
- Hormonal regulation
What are the mechanisms of renal auto regulation?
- Myogenic mechanism
- Tubuloglomerular regulation
What is the myogenic mechanism of renal Autoregulation?
Occurs when stretching triggers contraction of smooth muscle cells in Afferent arterioles- reducing GFR
What is the tubuloglomerular mechanism of renal autoregulation?
Macula densa cells provides feedback to glomerulus, preventing the Juxtaglomerular apparatus cells from releasing nitric oxide( NO)
This leads to constriction of Afferent arterioles which decreases GFR
Contrast the myogenic and tubuloglomerular mechanism of renal autoregulation?
Normalizes renal blood flow and GFR within seconds after a change in Blood pressure or acts more slowly than myogenic mechanism
Explain how hormonal regulation can reduce GFR
Angiotensin 2 reduces GFR- a potent vasoconstrictor of both Afferent and efferent arterioles
Explain how hormonal regulation leads to increase GFR
Stretching of atria causes release of Atrial Natiuretic Peptide( ANP) and causes relaxation of intra-glomerular mesangial cells, increases capillary surface area for filtration
Explain neuroregulation
-kidney blood vessels supplied by sympathetic ANS fibers that release norepinephrine causing vasoconstriction
Moderate stimulation- both Afferent and efferent arterioles constrict to same degree and GFR decreases SLIGHTLY
Greater stimulation- construction of Afferent arterioles predominates, blood flow into the glomerular capillaries is greatly decreased and GFR drops
What are the 3 main pressures Glomerular filtration depend upon?
One pressure promotes filtration and two pressures oppose filtration
- Glomerular blood hydrostatic pressure(GBHP)
- Capsular hydrostatic pressure(CHP)
- Blood colloid osmotic pressure (BCOP)
What is Glomerular Hydrostatic pressure
The blood pressure in Glomerular capillaries
What is Capsular hydrostatic pressure
Hydrostatic pressure exerted against filtration membrane by fluid already in the capsular space and renal tubule
What is the Blood colloid osmotic pressure BCOP?
Pressure due to presence of proteins in blood plasma
What is the net filtration pressure?
Total pressure that promotes filtration
What is the mathematical formula of net filtration pressure?
NFP= GBHP- CHP-BCOP
What are reabsorption routes?
- Paracellular Reabsorption
2. Transcellular Reabsorption
What is paracellular Reabsorption?
Fluid can leak BETWEEN the cells in a passive process in proximal convoluted tubules
What is transcellular reaabsorption?
Substance passes from the tubular lumen THROUGH the apiical membrane of a tubule cell, across the cytosol, and out into interstitial fluid through the base lateral membrane
What is primary active transport?
Energy derived from hydrolysis of ATP is used to”pump” a substance across a membrane; the sodium-potassium pump is one such pump
What is secondary active transport?
Energy stored in an ions electrochemical gradient, rather than hydrolysis of ATP , drives another substance across a membrane
What are symporters?
Are membrane proteins that move two or more substances in the same direction across a membrane
What are antiporters?
Move two or more substances in opposite directions across a membrane
What is facultative water reabsorption?
Reabsorption of the final 10% of the water
Regulated by ADH and occurs mainly in the collecting duct
What regulates facultative water Reabsorption? Where does it Occur?
ADH
In the collecting ducts
What is obligatory water Reabsorption?
Water reabsorbed with solutes in tubular fluid because water is “obliged” to follow the solutes when they are reabsorbed
Where does obligatory water Reabsorption occur?
Proximal convoluted tubule and descending limb of the nephron loop
Where does the largest amount of solute and water Reabsorption from filtered fluid occur?
In the proxi,al convoluted tubule
How much of each substance is reabsorbed in the proximal convoluted tubule?
About 65% of filtered water, sodium and potassium
100% of most filtered organic solutes e.g. glucose and aa’s
80%-90% of filtered bicarbonate- an important buffer
Describe tubular fluid at the end of the PCT
Tubular fluid is still isosmotic to blood (300 mOsm/liter)
List 4 sodium symporters
- glucose
- amino acids
- phosphate.
- sulphate
What are reabsorbed in the loop of henle
15% of filtered water and 20-30% filtered sodium and potassium
For the first time Reabsorption of water is NOT automatically coupled with solute Reabsorption when in the loop of henle. Why?
Part of the loop of henle is impermeable to water
Why is little or no water absorbed in the ascending limb?
Osmolarity progressively decreases as fluid moves towards end of ascending limb
Where does the PTH stimulate Reabsorption of calcium ions?
The early distal convoluted tubules
Describe substance Reabsorption in late distal convoluted tubule
Early DCT reabsorb about 10%-15%of the filtered water
Same symporters as ascending loop of henle
Na+ Cl- Symporters reabsorb Na+ and Cl-
Describe Reabsorption and secretion in late distal convoluted tubule and collecting duct
- 90-95% of filtered solutes and fluid have been returned by now
- Amount of water and solute Reabsorption and secretion depend on body needs
- Principal cells reabsorb Na+ and secrete K+
- Intercalated cells reabsorb K+ and HCO3- and secrete H+
How do principal cells reabsorb Na+ and secrete K+?
Sodium leakage channels in apical membranes of principal cells rather than symporters or antiporters
What is the role of Aldosterone in Hormonal regulation?
Na+ Reabsorption and K+ secretion in the late distal tubule and collecting duct
Explain the role of Angiotensin 2 in hormonal regulation
- Increases absorption Na+, Cl- and water I’m PCT by stimulating Na+/H+ antiporters
- Constricts Afferent arteriole, decreasing GFR
- Stimulates aldosterone release from adrenal cortex
What is the role of Atrial natriuretic peptide?
- Decreases Na+ Reabsorption in Proximal Convoluted Tubule and collecting duct
- Also increases GFR, increases blood volume causes stretch in right atrium and release of ANP
What is the role of PTH hormone?
- Increases Ca 2+ Reabsorption in DCT
- Decreases HPO4 2- Reabsorption
Describe the formation of dilute urine
- Osmolarity of interstitial fluid of renal medulla becomes greater, more water is reabsorbed from tubular fluid so fluids become more concentrated
- water cannot leave in thick portion of ascending limb but solutes e.g. Na-K-Cl leave making fluid more dilute than. Blood Plasma
- other solutes, little warter leaves in DCT. Low ADH makes late DCT and collecting duct have low water permeability
What are the 3 major solutes that contribute to the concentration of urine?
Na+, Cl- and urea
How concentrated can urine become?
4 times more concentrated than blood plasma
What does the ability of ADH depend on?
Presence of osmotic gradient in interstitial fluid of renal medulla
What are the 2 factors build and maintain gradient?
Countercurrent multiplication
Countercurrent exchange
What is countercurrent exchange?
Process by which solutes and water are passively exchanged between the blood of the vasa recta and the interstitial fluid of the medulla as a result of countercurrent flow.
What is the countercurrent multiplication?
The process by which a progressively increasing osmotic gradient is formed in the interstitial fluid of the renal medulla. Differences in solute and water permeability in different sections of loop of henle (countercurrent multiplication) and collecting duct
What can urinalysis be used to anakyze?
- analysis of volume and physical
- water, electrolytes, solutes, exogenous substances
What are 2 main ways in evaluating kidney function aside urinalysis?
Blood tests
Renal plasma clearance
What are two blood tests used to evaluate kidney function?
- Blood urea nitrogen (BUN)
- plasma creatinine
Explain renal plasma clearance
A substance that is filtered but neither reabsorbed or secreted has a clearance that equals GFR. Nearly the case with creatinine which is not absorbed and barely secreted
Explain the mictruition reflex
When the volume of urine in the urinary bladder exceeds 200-400ML pressure stretch receptors in its wall transmit nerve impulses into the spinal cord
These impulses propagate to the mictruition center in sacral spinal cord segments S3 and S4 and trigger a spinal reflex
What are the parasympathetic impulses of the mictruition impulses?
The nerve impulse lead to contraction of detrisor muscle and relaxation of the internal urethral sphincter muscle
What is the role of mictruition on somatic nerves for urination?
- Micturition center inhibits somatic motor neurons that innervates skeletal muscle in the external sphincter
- On contraction of the urinary bladder wall and relaxation of the sphincters, urination
Give the formula of renal plasma clearance
S= (U xV)/P
U- urine(concentration unit- mg/mL)
V- urine flow rate (unit is mL/min)
P- plasma concentration (mg/mL)
What substance is often used in renal plasma clearance?
Creatinine
Why does creatinine used for renal plasma clearance have the same GFR?
All the molecules that pass the filtration membrane appear in the urine
What stimulates angiotensin 2 secretion?
Decreased blood pressure
What does angiotensin 2 cause and where in the nephron does it stimulate?
Increased GFR, Filtered fluid
Increased Na+ Reabsorption in proximal and distal convoluted tubule
Preservation of renal function in low volume state
Also affects thick nephron and efferent arterioles
What is the effect of Atrial natriuretic peptide on the nephron, where does it affect?
Increases GFR and Na+ filtration to decrease Na+ and volume of fluid
Affects Afferent arterioles and distal convoluted tubule
What is the effect of parathyroid hormone in the nephron, where does it take affect?
Causes increase in calcium Reabsorption in the distal convoluted tubule
Phosphate ion in the proximal convoluted tubule
Active vitamin d production
(Ca2+ and phosphate ion absorption via vitamin D)
What is the effect aldosterone on the nephron and where does it have its effect?
Causes Na+ absorption, k+ and h+ secretion
What causes aldosterone secretion?
Low blood volume and high plasma potassium
What is the effect of ADH / vasopressinon the nephron and where does it take effect?
Binds to principle cells causing increase in aquaporrins for water Reabsorption
Increase in urea to increase corticocapilkary osmotic gradient
