What is the primary role of the kidneys?
What are their specific functions?
- To maintain the volume and composition of body fluids despite wide variation in daily intake of water and solute
- Regulate water and inorganic ion balance (osmolarity)
Balance acid/base equilibrium
Eliminate metabolic waste products (i.e. urea, uric acid, creatinine)
Eliminate foreign compounds
Gluconeogenesis
Secrete hormones
Draw and label the Lobule of the kidney. Where is it located?
The lobule of the kidney is centered on the Medullary Rays
What are the functional units of the kidney called?
Nephrons
Which 2 cell types make up the collecting duct, and what are their functions?
- Principal cells - NaCl reabsorption and K+ secretion
- Intercalated cells - acid-base balance
Define Renal Lobe
A single pyramid with is overlying cortex
Define Renal Lobule
A single medullary ray with adjacent cortical labyrinth.
A functional unit that consists of collecting duct and all the nephrons that it drains
What is the function of the renal cortex?
site of glomerular filtration
What is the function of the renal medulla?
Drainage of collecting ducts into renal pelvis and ureter
Name the vessels of renal veins in order of fluid flow
Renal vein → Interlobular vein → arcuate vein → interlobular vein → stellate veins
note that the ascending vasa recta branches off from the arcuate vein as does the interlobular vein
vasa recta is located in the pyramid of the medulla
Name the vessels of renal arteries in order of fluid flow
Renal artery → interlobar artery → arcuate artery → interlobular artery → afferent arteriole → superficial glomerulus → efferent arteriole → peritubular capillary beds
note that the efferent arteriole of the juxtamedullary glomerulus becomes the descending vasa recta
vasa recta is located in the pyramid of the medulla
Name the sections of the renal tubules in order starting with Bowman’s Capsule
Bowman’s Capsule → proximal convoluted tubule → descending loop of Henle → thick ascending loop of Henle → macula densa (cells) → distal convoluted tubule → cortical collecting duct → outer medullary collecing duct → inner medullary collecting duct → papillary duct (duct of Bellini)
How is the Medullary Ray defined?
It sits right at the border between the cortex and the medulla and it encompasses only straight tubules (from the loops of Henle and the collecting tubule)
Renal Hilum
Area where blood vessels and nerves enter and exit the kidney. Concaved part of the “bean shape”
Approximately how many nephrons are there/kidney?
1 million
Which structures make up each nephron?
a “tuft of capillaries” and a renal tubule, which forms a cup shape around the capillaries
- glomerular capsule/Bowman’s capsule
What are the 2 types of nephrons and what are their primary characteristics?
- Cortical nephron
- most nephrons are in this category (85%)
- have short loops of Henle - Juxtamedullary nephron
- the glomeruli of these nephrons are found at the border between the cortex and medulla
- have long loops of Henle
- heavily involved in urine concentration
- make up 15% of nephrons
What are the sections of the medulla and how are they defined?
Outer Medulla
- outer stripe: thick tubular segments and outer medullary collecting ducts
- inner stripe: thick and thin tubular segments and outer medullary collecting ducts
Inner Medulla
- thin tubular segments and inner medullary collecting ducts
What makes up the Renal Corpuscle?
The glomerulus and Bowman’s Capsule
Describe the orientation of the epithelial cells that line the renal tubules
The luminal membrane of the cells faces the lumen of the tubule, while the basolateral membrane of the cells is in contact with interstitial fluid and peritubular capillaries.
There are tight junctions between these cells.
What lines Bowman’s Space?
Bowman’s space is surrounded by 2 epithelial layers
What are the 2 Fluid-filled spaces of the Renal Corpuscle, and what makes up the fluid that fills each of them?
Describe the function of the space if specific
Vascular Space
- structure: glomerular capillaries
- fluid: plasma, RBCs, WBCs, proteins, electrolytes, etc
Urinary Space
- structure: Bowman’s space (lined by 2 epithelial layers)
- fluid: ultrafiltrate plasma
- function: this is the first step in urine formation
Name the cells that make up the vascular pole of a Renal Corpuscle and state where they are located (in relation to other structures)
Macula densa cells are found near the distal convoluted tubule
Smooth muscle cells line the afferent and efferent arterioles
Juxtaglomerular cells
Extraglomerular mesangial cells
Mesangial cells
Foot processes (pedicels) of podocytes
Name the cells that make up the urinary pole of a Renal Corpuscle and state where they are located (in relation to other structures)
Podocyte (visceral layer)
Parietal layer (Bowman’s Capsule)
Name the functions of Mesangial Cells
- Provide mechanical support
- Control GBM material turnover
- Regulate blood flow
- Secrete vasoactive substances
- Respond to angiotensin II
Describe the structure of a podocyte
The podocyte is part of the visceral layer. It is comprised of a cell body, primary process, secondary process, and pedicels (branch from secondary processes). It is lined internally by the basal lamina and a layer of endothelial cells of the glomerulus. Between podocyte processes are filtration slits.
What is the function of a podocyte?
The final passage of fluid from the glomerular capillary to Bowman’s space occurs through the filtration slits between the pedicels of the podocyte.
Podocytes surround glomerular capillaries and provide structural support
Foot Processes surround the basement membrane and are responsible for podocyte termination
Filtration Slits are clefts between foot processes where filtrate enters Bowman’s space
Name the structure that comprise the Glomerular Filtration Barrier (excluding cells, proteins, and large molecules)
Vascular Space - glomerular capillary endothelium
Shared Space - basement membrane (filtration membrane)
Tubular Space - Podocytes and Bowman’s Capsule
- Podocytes are epithelial cells, which all other cells are endothelial
What role do glomerular capillaries play in filtration?
They are fenestrated to allow for the passage of solute-rich fluid. Proteins are typically excluded from passage due to their size, which results in a filtrate that is low in protein.
What are the primary proteins that comprise the filtration slit between podocytes?
Podocin
Nephrin
NEPH-1
What is the pathophysiological result of mutations in proteins comprising the filtration slit?
Proteinuria and Nephrotic Syndrome
What are some broad characteristics of the renal vasculature?
All blood that flows through the kidneys flows through glomeruli.
All glomeruli are located in the cortex
There are 2 types of capillary beds that exist in series
- glomerular capillaries (afferent and efferent arterioles)
- postglomerular capillaries (peritubular capillaries and vasa recta)
What forces are responsible for the movement of fluid and solute from the capillaries to Bowman’s Capsule?
Fluid moves by bulk flow due to high hydroststic pressure caused by the afferent and efferent arterioles, which only feed and drain a relative small volume of capillaries
What happens to most of the filtrate that moves into Bowman’s Capsule?
It is reabsorbed by renal tubules and returned to the blood through peritubular and vasa recta capillaries
What is the function of the primary cilia found in proximal tubules of the kidneys?
Mechanosensor - sense changes in flow rate of tubule fluid
Chemosensors - sense/respond to compounds in surrounding fluid
They initiate calcium-dependent signalling pathways involved in kidney cell function, proliferation, differentiation, and apoptosis
What structures make up the juxtaglomerular apparatus?
The macula densa cells at the top of the thick ascending limb of the loop of Henle come into close proximity with the afferent arteriole of the same nephron
Cells that make up the apparatus:
- macula densa cells (of thick ascending limb of loop of Henle)
- juxtaglomerular cells (of afferent arteriole)
- extraglomerular mesangial cells
What is the primary secretion of the juxtaglomerular apparatus?
Renin, which is an endocrine signal
What are the structural characteristics and functions of the Juxtaglomerular cells (granular cells) in the afferent arteriole?
Mechanoreceptors - stretch receptors sense stretch in the afferent arteriole, innervated by the sympathetic nervous system
Renin is stored in secretory granules held in enlarged smooth muscle cells
Cells are part of the Renin-angiotensin system (RAS), which raises blood pressure
What are the structural characteristics and functions of the Macula Densa cells of the TAL?
Tall, closely packed, tubular epithelial cells that are adjacent to granular JG cells
Chemoreceptors respond to changes in NaCl content of filtrate
Cells are critical regulators of Blood Pressure. They work in tandem
What are the structural characteristics and functions of the Glomerular Mesangial Cells?
They are smooth muscle-like cells
They help regulate blood flow in the glomerulus by contraction
They engulf macromolecules that get hung up during filtration
What is the primary function of the loops of Henle?
They are responsible for establishing the interstitial osmotic gradient
They are a countercurrent multiplier
What is the function of renal circulation?
It is responsible for:
- Returning reabsorbed solutes to circulation and maintaining hyperosmotic interstitial medulla
- Concentrating Urine - countercurrent exchange system
What is the primary function of the juxtaglomerular apparatus?
Regulating blood pressure
Define tonicity and describe the outcomes for cells that are hypertonic and hypotonic
Tonicity - ability of solute to cross cell membrane (relative concentration of solute on each side of membrane). Refers to the solution surrounding the cell.
Hypertonic causes cell to shrink
Hypotonic causes cell to swell
Define osmole
The amount of substance that dissociates in solution to form 1 mole of osmotically active particles
i.e. 1 mole of NaCl = 2 osmoles of solute
Define osmolality
osmoles/kg H2O
- completely dependent on the # of molecules in the solution
- Normal value for body fluids: 290 mOsmoles/kg solution
Define osmolarity
osmoles/L solution
*In dilute solutions, the osmolality ~ osmolarity
What is the normal range and concentration in plasma/cell of Na+?
(in mmol/L)
Normal Plasma Range - 135-145
Plasma Concentration - 142
Cell - 15
What is the normal range and concentration in plasma/cell of K+?
(in mmol/L)
Normal Plasma Range - 3.5-5.0
Plasma Concentration - 4.4
Cell - 140
What is the normal range and concentration in plasma/cell of Ca2+?
(in mmol/L)
Normal Plasma Range - 1.14-1.3
Plasma Concentration - 1.2
Cell - 100 nM
What is the normal range and concentration in plasma/cell of H+?
(in pH)
Normal Plasma Range - 7.38-7.42
Plasma pH - 7.4
Cell - ~7.2
What is the normal range and concentration in plasma/cell of Cl-?
(in mmol/L)
Normal Plasma Range - 100-108
Plasma Concentration - 102
Cell - 10
What is the normal range and concentration in plasma/cell of HCO3-?
(in mmol/L)
Normal Plasma Range - 22-28
Plasma Concentration - 24
Cell - 10
What is the normal range and concentration in plasma/cell of Protein?
(in g/dl)
Plasma Concentration - 7
Cell - 40
What is the normal range and concentration in plasma/cell of Glucose?
(in mg/dl)
Normal Plasma Range - 70-110
Plasma Concentration - 100
What is the normal range for and plasma/cell osmolality?
(in mosmol/kg H2O)
Normal Plasma Range - 285-295
Plasma Concentration - 290
Cell - 290
What is the most abundant substance in the body?
Water
What types of fluid make up extracellular fluid?
Interstitial fluid, intravascular compartment fluid, lymph, and transcellular fluid
What volume of fluid is contained in the 3 primary fluid compartments?
What is the total body water (TBW)?
Interstitial Fluid - 11 L
Intracellular Fluid - 28 L
Plasma - 3 L
Total Body Water - 42 L
What is the equation for Total Body Water (TBW)?
TBW = 0.6 x Body Weight
What is the breakdown of the components of Total Body Water?
What is the percentage breakdown of fluids comprising total body water?
Total Body Water = 60% of body weight
Intracellular Fluid = 40% of body weight
Extracellular fluid = 20% of body weight
What is the water content of adipocytes and muscle cells?
adipocytes - 10%
muscle cells - 76%
What is the breakdown of the components of Extracellular fluid?
Interstitial Fluid = 75% of ECF
Plasma Volume = 20% of ECF
Transcellular Fluid = 5% of ECF
- transcellular fluid includes
pericardial
pleural
digestive secretions
synovial
cerebrospinal
intraocular
bile
peritoneal
cochlear
sweat
renal tubular
What is the general breakdown of cation and anion concentration between ECF and ICF
What allows water to diffuse freely across semipermeable membranes?
aquaporins
How does volume and osmolarity change when an isotonic solution of NaCl is given intravenously?
ECF volume is increased
osmolarity is unchanged
How does volume and osmolarity change when a hypotonic solution of NaCl is given intravenously?
extracellular volume increases
intracellular volume increases
extracellular and intracellular osmolarity decreases
How does volume and osmolarity change when a hypertonic solution of NaCl is given intravenously?
extracellular volume increases
intracellular volume decreases
osmolarity increases
Name the primary renal processes and which compartments are involved in the fluid transfer?
Glomerular Filtration:
glomerular capillary lumen ⇒ Bowman’s space (bulk flow)
Tubular Reabsorption:
tubular lumen ⇒ peritubular capillary plasma
Tubular Secretion:
Peritubular plasma (capillary lumen) ⇒ interstitial space ⇒ tubular cell ⇒ tubular lumen (tubular cell interior to tubular lumen)
Drug Handling by the Kidney
Define Renal Clearance
The volume of plasma from which a substance is completely removed (cleared) by kidneys per unit time
ml/min
- compares the rate of glomerular filtration to the rate at which the kidneys excrete the substance into the urine
- it is a quantitative measure of how kidneys handle a single substance
What is the gold standard measure of GFR (glomerular filtration rate)?
Inulin
- it is the gold standard because the amount of inulin filtered = the amount excreted.
Equation: GFR = (UIN x Volume/time)/PIN = CIIN
What are the relevant characteristics of Inulin?
- Freely filterable
- Not reabsorbed
- Not secreted
- Not metabolized, synthesized, or stored
- Do not alter GFR
- nontoxic
- Infusion is required
What is a secondary, but standard, measure for GFR?
Creatinine
- CICr ~ GFR
- The rate of production of creatinine roughly equals the rate of excretion
Equation for Index of GFR: GFR = (UCr x Volume/time)/PCr
What are the relevant characteristics of creatinine?
- Metabolism of creatinine phosphate in the muscle
- Produced continuously
- Freely filtered
- Not reabsorbed
- About 10% is secreted by PT
- No infusion is required
- Stable P[Cr]
- P[Cr] and U[Cr] are colorimetric method
- Plasma creatinine is inversely related to GFR
What is the normal plasma concentration of creatinine and normal GFR?
PCr = 1 mg/dl
GFR = 125 ml/min
How is Renal Plasma Flow measured?
PAH - Para-amino hippuric acid
ClPAH ~ RPF
Equation: ClPAH = RPF = (UPAH x Volume/min)/PPAH
What are the relevant characteristics of PAH?
- Organic anion
- Freely filtered
- Vigorously secreted (PT)
- Greater than 90% removed in a single circuit
- About 10% remains in the RV
- Not produced naturally
- Infusion required
How are Renal Clearances determined?
Clx < GFR – net reabsorption x
Clx > GFR – net secretion x
Clx < ClIN – reabsorbed (i.e. glucose)
Clx > ClIN – secreted (i.e. PAH)
- protein-bound drug is not filtered
- if the filtered load > rate of excretion = reabsorption of X
Define oncotic pressure
π; mmHg
The pressure generated by large molecules (especially proteins) in solution
Define Hydrostatic Pressure
P; mmHg
The pressure exerted by liquids
RAP
Renal Artery Pressure
What is the equation for Starling Forces?
Gives a measure of the volume flux across a capillary wall. Net Starling Forces = PUF
Jv = Kf*[(Pc - Pi) - σ(πc - πi)]
- Kf = Ultrafiltration Coefficient for Glomerular Capillaries (ml/min/mmHg). This is a measure of the intrinsic permeability of the glomerular capillary. It is a product of the Hydraulic Conductivity (LP) and the Surface area (Sf).
10-100x > other capillary beds
- σ = Reflection Coefficient for Glomerular Capillaries (for protein, σ = 1. 100% reflection)
- Starling forces are ultimately responsible for fluid filtration from the glomerular capillaries
- Starling forces favor net filtration towards the arterioles and net absorption towards the venules
- Overall, filtration is roughly equal to absorption
Regarding Starling Forces, which 2 forces favor filtration?
Substances are filtered from the glomerular capillaries to Bowman’s Space.
PGC (Hydrostatic pressure in the Glomerular Capillaries)
πBS (Oncotic pressure in Bowman’s Space)
Regarding Starling Forces, which 2 forces oppose filtration?
PBS (hydrostatic pressure in Bowman’s Space)
πGC (oncotic pressure in the glomerular capillaries
What is the Glomerular Filtration Rate for normally functioning kidneys?
125 ml/min (for both kidneys)
What is the equation for Net Filtration Pressure (NFP)?
NFP = PGC - PBS - πGC + πBS
πBS = 0 mmHg because proteins cannot pass membranes into Bowman’s Space from Glomerular Capillaries
**PGC is about 2X greater than other capillaries
What is filtered into Bowman’s Space as Glomerular Ultrafiltrate?
electrolytes, water
*Plasma concentration = Bowman’s Space concentration
Where does net absorption occur?
peritubular capillaries due to change in Starling Forces traveling along the capillaries
What are the renal parameter values for Cardiac Output and Renal Blood Flow?
Cardiac Output - 5000 ml/min
Renal Blood Flow - 1000 ml/min
What is the renal fraction of blood flow?
RBF/CO
20%
What is renal plasma flow rate?
RBF x (1-Hct)
600 ml/min
What is the renal filtration fraction?
GFR/RPF
20%
What is the urine flow rate in a normal person?
1 ml/min
1 ml/kg/hr urine output
How can one determine the amount of fluid reabsorbed?
GFR - V (urine flow rate)
i.e. in a normal person, GFR = 125 ml/min and V = 1 ml/min
therefore, fluid reabsorbed = 125 - 1 = 124
99% of fluid is reabsorbed!
Fluid Filtration is much much much greater than Urine Output
How does oxygen consumption in the kidney compare to oxygen consumption in the other tissues of the body?
O2 consumption/g(tissue) in the kidney is greater than any other tissue in the body except the heart
The difference between the venous oxygen and arterial oxygen content is much lower because SO MUCH blood is pumped through the kidneys. Therefore, oxygen is not a critical factor for regulating renal blood flow.
What needs to happen in order to decrease both GFR and RBF?
Increase resistance in the afferent arterioles
What needs to happen in order to increase GFR and decrease RBF?
increase resistance in the efferent arteriole
*This ultimately diverts blood flow to other organs
What needs to happen in order to decrease GFR and increase RBF?
dilate efferent arterioles
What needs to happen in order to increase GFR and RBF?
dilate afferent arteriole
Describe the general concept of intrinsic Renal Blood Flow regulation
autoregulation - the vascular bed maintains renal blood flow by controlling blood pressure
This is done without hormones, nervous system input, and without a metabolic component
What is normal RAP (Renal Arterial Pressure)?
~90-180 mmHg
This is maintained using changes in afferent arteriole resistance only!
As RBF and GFR increase, afferent arteriole pressure also increases (keeping the pressure the same)
Describe the intrinsic myogenic mechanisms of autoregulation
Based on an intrinsic property of arterial vascular smooth muscle cell
- increased stretch in the vascular wall causes muscle cells to contract
- decreased stretch in the vascular wall causes muscle cells to relax
Describe the intrinsic Tubuloglomerular Feedback (TGF) mechanism of autoregulation
When GFR increases, the flow through tubules increases. This results in an increased filtration of NaCl, which is sensed by Macula Densa cells (part of the distal convoluted tubule).
The macula densa cells secrete ATP or adenosine in paracrine mechanism to the afferent arteriole.
This causes the afferent arteriole to constrict, which decreases hydrostatic pressure in the glomerulus and decreases GFR (returns to normal)
How is extrinsic control of Renal Blood Flow accomplished?
There is NO parasympathetic innervation.
Juxtraglomerular cells release norepinephrine, which increases firing rate in response to things like dehydration, fear, pain, trauma, shock. This leads to vasoconstriction and decreases RBF and GFR.
**This mechanism can override the intrinsic autoregulation mechanisms
What is AVP/ADH and how do they work?
AVP = Arginine Vasopressin
(it is the same peptide as ADH - antidiuretic hormone)
These two hormones are identical, but have different functions due to localization of specific receptor types and hormone release
These hormone ultimately cause the arterioles to contrict, which reduces RBF and GFR. This decreased blood flow through the renal medulla increases medullary interstitial osmolarity (because there isn’t fluid being filtered into the interstitial cavity?), which increases water reabsorption, and therefore increases blood pressure
What are ANP/BNP and how do they work?
Atrial/Brain Natiuretic Peptide
They are secreted by the cardiac atria (ANP) and ventricles (BNP) in response to atrial distension, increased plasma volume, and severe volume expansion.
Release causes dilation of afferent arterioles and constriction of efferent arterioles. This increases or maintains RBF and increases GFR.
What is the RAS system, and how does it work?
Renin-antiotensin system
It regulates Na+ balance and plasma volume, which in turn helps to regulate arterial blood pressure
Starts as inactive precursor, and Renin is the rate-limiting factor in angiotensin II formation (angiotensinogen ⇒ angiotensin I ⇒ (via angiotensin converting enzyme) angiotensin II (active)
Results - vasoconstriction and aldosterone secretion (increased absorption of sodium and secretion of potassium)
**Primarily concerned with increasing extracellular fluid volume and increasing mean arterial blood pressure
What are the hemodynamic actions of Angiotensin II?
- afferent and efferent arterioles are constricted, causing reduced RBF
- mesangial cells contract, which reduces Kf and GFR
- increased sensitivity to tubuloglomerular feedback
- decreased medullary blood flow
- ultimately reduced RBF and GFR
Tell me about endothelin
Endothelin is both an intrinsic and extrinsic regulator that helps generate endothelial, mesangial, and tubular cells
It is secreted in response to shear stress, angiotensin II, and catecholamines
It constricts vascular smooth muscle cells of the afferent and efferent arterioles, which decreases both RBF and GFR
Tell me about Nitric Oxide
Nitric Oxide (NO) is both an intrinsic and extrinsic regulator that is produced by endothelial cells in response to shear force, acetylcholine, histamine, and bradykinin.
It relaxes vascular smooth muscle, which dilates afferent and efferent arterioles to help buffer excessive vasoconstriction by angiotensin and norepinephrine. It decreases Total Peripheral Resistance (TPR)
Tell me about Renal Prostaglandins
They are both intrinsic and extrinsic regulators, including PGE1, PGE2, and PGI2
Release results in vasodilation of afferent and efferent arterioles, which results in increased RBF and GFR. Their primary purpose is to buffer excessive vasoconstriction
Increase in severe volume depletion - dehydration, salt depletion, blood loss (hemorrhage), low BP, surgery, anesthesia, stress, activation of SNS, and RAS
State the hormones that increase GFR and RBF and those that decrease GFR and RBF
Increase GFR and RBF
Angiotensin II
Endothelin
AVP (arginine vasopressin)
RSNA (sympathetic nervous system?)
Decrease GFR and RBF
Prostaglandins
NO
Bradykinin
Natiuretic Peptides
What are the 3 basic processes in urine formation?
- ultrafiltration of plasma by the glomerulus
- reabsorption of water and solutes from the ultrafiltrate
- secretion of select solutes into the tubular fluid
What is the equation to determine amount of sodiume excreted?
amount excreted/min - amount reabsorbed/min
GFR - tubule transport (these are tightly regulated)
ANOTHER EQUATION
Excretion = Filtration - Reabsorption + Secretion
What are some of the organic anions secreted by the proximal tubule?
Cyclic AMP, cyclic GMP
Bile Salts
Hippurates
Oxalate
Prostaglandins: PGE2, PGF2alpha
Urate
Vitamins: ascorbate, folate
What are some of the organic cations secreted by the proximal tubule?
Creatinine
Dopamine
Epinephrine
Norepinephrine
What are the percentages of Sodium reabsorption by section of the renal tubules?
Proximal Convoluted Tubule: 67%
Thick Ascending Limb of the Loop of Henle: 25%
Distal Convoluted Tubule: 4%
Cortical Collecting Duct: 3%
Inner Medullary Collecting Duct: 1%
Define solvent drag
When solutes dissolved in water are carried across membranes with water
What are some examples of symport mechanisms in the kidneys?
Proximal Tubule
Sodium-glucose
Sodium-amino acid
Sodium-inorganic phosphate
Thick Ascending Limb
Sodium-Potassium-Chloride
What are some examples of antiport mechanisms in the kidneys?
Proximal Tubule
Sodium-Hydrogen ion (apical membrane)
Where is the sodium potassium ATPase pump located in kidney cells?
basolateral membrane
What are some examples of active transport in the kidneys?
Basolateral Membranes
Sodium-potassium ATPase
H+ Secretion in Collecting Duct
Hydrogen Ion ATPase
Hydrogen Ion-Potassium ATPase
Movement of calcium from cell cytoplasm into blood
Calcium ATPase
How are small proteins and macromolecules reabsorbed by the proximal tubule?
endocytosis
What is the transcellular pathway for substance reabsorption/secretion?
though cells
What is the paracellular pathway for substances reabsorbed/secreted?
between cells through lateral intercellular spaces (beneath tight junctions)
How is sodium reabsorbed in the proximal tubule segment of the nephron?
Sodium-Potassium ATPase pump
- located exclusively on the basolateral membrane
- the active movement of sodium OUT of the cell keeps the concentration low in the cell. This creates the concentration gradient necessary for sodium to move from the tubules into the cell (which is then pumped out)
- the internal environment of the cell is also more negative than the lumen of the tubule, which further drives sodium movement into the cell
Which nephron segment reabsorbs virtually all of the glucose and amino acids filtered by the glomerulus?
The proximal tubule
What are the primary mechanisms for sodium reabsorption in the first and second half of the proximal tubule?
First Half
sodium transport into cell coupled with the movement of H+ out of the cell (NHE3 antiporter) or other organic solutes
- sodium moves along with bicarbonate, glucose, amino acids, inorganic phosphate, lactate
- it looks like bicarbonate is being reabsorbed into the blood as sodium bicarbonate
Second Half
Sodium is primarily reabsorbed trancellularly along as NaCl
- sodium enters the cell through Na+-H+ antiporters and Cl–base antiporters
- sodium enters the blood through the sodium-potassium ATPase pumps
What happens to the chloride concentration in the ultrafiltrate as you move along the tubule?
The concentration of chloride increases because more water than chloride is reabsorbed in the first half of the proximal tubule
How does chloride reenter circulation from the cells in the second half of the proximal tubule?
K+-Cl- symporter
Cl- channel in the basolateral membrane
paracellular route due to the concentration gradient created in the first half of the proximal tubule
*movement of chloride through the paracellular route causes the voltage across the epithelial layer to be more positive on the tubular side (because the cloride is leaving), which causes sodium to leave and enter circulation through a paracellular route as well
- this, again, causes an osmotic gradient and the passive reabsorption of water
Define diuretics
drugs that increase the net excretion of water from the body by:
- interfering with renal tubular reabsorption of sodium and consequently water
- antagonizing the hydroosmotic effect of vasopressin (antidiuretic hormone)
What type of drug is mannitol and what is its mechanism of action?
Mannitol is an osmotic diuretic that works along the entire tubule
It is a large molecule that is filtered at the glomerulus and creates an osmotic gradient that favors the movement of water into the tubular lumen.
What is the threshold for glucose reabsorption in the tubules?
200 mg/dl until glucose starts to be excreted in the urine
What kind of drug is Acetazolamide and what is its mechanism of action?
Acetazolamide is a carbonic anhydrase inhibitor that works in the proximal tubule (which is where the bicarbonate is reabsorbed along with sodium)
3 bicarbonates/sodium
- blocks sodium reabsorption by preventing the creation of Hydrogen ions used as part of the sodium-hydrogen ion antiporter
Which electrolytes are reabsorbed in the thick ascending limb of the loop of Henle, and how are they transported?
sodium-chloride (2) -potassium transporter from the luminal membrane to the cell
Potassium also diffuses out of the cell back into the lumen
sodium-hydrogen ion transporter on the luminal membrane
Bicarbonate transported to blood w/ sodium
sodium-potassium ATPase pump
potassium and chloride cotransported into the blood
What is furosemide and what is its mechanism of action?
Furosemide is a high-ceiling or loop diuretic that works at the thick ascending limb of the loop of henle.
- it blocks the sodium-chloride-potassium transporter, which prevents the reabsorption of sodium (as well as the other ions). This also blocks calcium and magnesium reabsorption because they typically are reabsorbed through the paracellular route due to the movement of chloride from the tubule lumen into the interstitial fluid
What is hydrochlorothiazide and what is its mechanism of action
Hydrochlorothiazide is an early distal tubule diuretic that blocks the sodium-chloride cotransporter, increasing sodium and chloride excretion
- Under normal conditions, after the sodium and chloride are transported across the apical membrane, chloride and potassium are transported via the same transporter across the basolateral membrane.
What is the primary adverse effect of loop diuretics and thiazides?
hypokalemia because potassium cannot be reabsorbed
What is Amiloride and what is its mechanism of action?
ENaC blockers work in the collecting ducts and promote the excretion of sodium (and water) by preventing the reabsorption of sodium through the cells of the collecting ducts
- prevent the secretion of potassium (and therefore hypokalemia) by inhibiting the production of products that are synthesized in response to the production of aldosterone. This prevents the activation of sodium/potassium exchangers
What is Spironolactone?
a potassium-sparing diuretic
- aldosterone receptor antagonist. Blocks aldosterone receptors
What is vasopressin and what is its mechanism of action?
Vasopressin (arginine vasopressin) is an anti-diuretic hormone in the collecting ducts that mediates water reabsorption
Examples are Tolvaptan (AVP V2 receptor antagonist)
Used for hyponatremia
In which section of the nephron is ADH absolutely required for water reabsorption?
In the inner medullary collecting duct
Where does the concentration of urine primarily occur?
In the descending limb of the loop of Henle
Where does urine dilution primarily occur?
in the ascending limb of the loop of Henle
What are the 3 most important aspects of the nephron for urine concentration and dilution?
- Anatomy (hairpin loops)
- Opposite flow
List the 3 parts of the countercurrent system
- countercurrent flow - anatomy
- countercurrent exchange - vasa recta
- fluid and ions exchanged between tubules and vasa recta vessels because they are close together (also anatomy) - countercurrent multiplication - tubules
- as you move down the descencing limb, the concentration of solute gets larger, resulting in hyperosmotic medullary interstitial fluid and prompting the return of fluid to the tubules after the hairpin loop
Describe how recycling of urea occurs in the kidney
(from the glomerulus)
- urea enters the tubules starting at the end of the proximal tubule into the descending limb of the loop of henle
- it continues to enter the tubules until the end of the thin ascending limb of the loop of henle, which increases oncotic pressure in the tubules
- in the collecting duct, high plasma levels of ADH promotes membrane permeability to water, but not to urea, which causes water to be reabsorbed and increases the concentration of luminal urea
- at the end of the collecting duct, the membrane is possibly also permeable to urea, which favors recycling of urea
