Renal Flashcards
What are the functions of the kidney?
Regulation of water, inorganic ion balance, and acid/base balance
Removal of metabolic waste products from the blood and their excretion in the urine
Removal of foreign chemicals from the blood and their excretion in the urine
Production of hormones/enzymes
What hormones/Enzymes are produced by the kidney? what do they do?
Erythropoietin (stimulates RBC production)
Renin (RAAS system, increases bp/Na balance)
1, 25 dihydroxyvitamin D: active vitamin (involved in Ca balance)
How is the kidney organized? How what veins/arteries are present?
Medullary Lobes, with cortical lobules Many nephrons (renal corpuscle, tubule)
Renal artery - Interlobar artery - arcuate artery - interlobular artery - afferent arteriole (reverse for veins) efferent arteriole - capillary - veins….
Describe the nephorn’s structures
Glomerulus Bowmans space (in bowman's capsule) Proximal convoluted tubule Proximal straight tubule Descending thin limb of Henle's loop Ascending thin limb of Henle's loop Thick ascending limb of Henle's loop Distal convoluted tubule Cortical collecting duct Medullary collecting duct Renal pelvis
What are the two layers of the renal corpuscle
Parietal layer (outside) Visceral layer (touching glomerulus, podocytes)
How is the nephron vascularized?
Peritubular capillaries
What are the three processes of urine production?
Glomerular filtration Tubular secretion (capillaries -> tubules) Tubular reabsorption (tubules -> capillaries)
What is filtered by glomerular filtration?
Water, low-moleculary weight substances
Cells, proteins, protein-bound substances do not cross
How do you calculate the amount of urine excreted?
Amount filtered + amount secreted - amount reabsorbed
What is the only substance that is not reabsorbed?
Para-amino-hippurate
True/False? In a healthy person, glucose never enters the nephron
False (enters nephron but is completely reabsorbed)
How is net glomerular filtration pressure calculated?
Glomerular Capillary blood pressure - Fluid pressure in Bowman’s Space - Osmotic force due to plasma proteins (oncotic pressure)
Usually: 60 - 15 - 29 = 16
What is the glomerular filtration rate? How is it controlled? Which of those methods is under physiological control?
What is a normal GFR?
The volume of fluid filtered from the glomeruli into Bowman's space per unit time Regulated by: Net Filtration rate (most important) Membrane Permeability Surface area Available for Filtration
Normal GFR = 180 L/day
How can you increase GFR? How can you increase it?
Increase: Constrict aferent arteriole or dilate eferent arteriole
Decrease: constrict eferent arteriole or dilate aferent arteriole
All methods control Glomerular capillary pressure (increasing GFR decreases Pgc, decreasing GFR increases Pgc)
What is filtered load? How is it calculated?
When is net reabsorption present? When is net secretion present?
Total amound of any free filtered substance per unit time
Filtered Load = GFR x plasma concentration of the substance
Filtered Load > amount excreted: absorption
Filtered Load < amount excreted: secretion
What is the differene between paracellular and transcellular reabsorption?
Transcellular: from tubular lumen to tubular epithelial cell (needs transport proteins) and then into peritubular capillary
Paracellular: directly from tubular lumen to peritubular capillary through tight junctions between epithelial cells
True/False? Filtered loads are typically quite small
False
True/False? Reabsorbtion of waste products is relatively incomplete
True
True/False? Reabsorption of the most useful plasma components is relatively incomplete
False
True/False? Reabsorbtion of some substances are completely unregulated
True (eg glucose, amino acids)
What are two methods of reabsorbtion?
Diffusion
Mediated transport
Where does water reabsorption take place?
Proximal tubule
What is typically associated with mediated transport?
Sodium reabsorption (for secretion and reabsorbtion)
How does mediated transport work for eg amino acids?
AA are brought into tubular epithelial cell (Na symporter - Na enters epithelial cell as well)
AAs leave through channels
Na/K ATP ase pumps Na into peritubular capillary and K into cell
What is a tranpsort maximum (Tm)
When the membrane transport proteins become saturated and the tubule cannot reabsorb the substance anymore
What are the two most important substances secreted by tubules?
Hydrogen ions and potassium
Where does ion reabsorption take place?
Henle’s loop
Where does solute secretion take place?
Proximal tubule
What is the purpose of the DCT and CD?
Fine tuning (small volume of water/solutes) determines final amounts excreted in urine
Homeostatic Controls are exerted here
What is clearance and how is it calculated?
The volume of plasma from which a substance is completely cleared by the kidneys per unit time
Clearance of S, C_S = (mass of S excreted/time)/Plasma concentration of S (P_S)`
What is Inulin? How is it used?
A polysaccharide that is administered intravenously to measure clearance
Inulin is freely filtered at the glomerulus but it is not reabsorbed, secreted, or metabolised
The clearance of inulin is equal to the volume of plasma originally filtered (C_IN = GFR)
What is Creatine? How is it used?
A waste product produced by muscle
Filtered freely at glomerulus and is NOT reabsorbed
It is secreted at the tubule but very minor, NOT metabolized
Thus, creatinine clearance is used as a clinical marker for GFR (a good approximation)
If urine volume is V,
Urine concentration of creatine is Ucr
and Plasma concentration of creatine is Pcr
How would you calculate GFR?
Creatine clearance ~ GFR = UcrV/Pcr
What happens if clearance of a substance is greater than GFR? What happens if it is less than GFR? What happens most often?
Clearance > GFR: secreted at tubule
Clearance < GFR: reabsorbed at tubule
Reabsorbtion is most common
How much water and sodium are secreted at the tubule?
None
Name the only location in the nephron where sodium reabsorption does not take place
The descending thin loop of Henle
Reabsorption of what substance is dependent on sodium reabsorption?
Water
How does sodium travel from the tubular lumen to the cortical collecting duct cells (i.e. at the apical membrane)
What about in the proximal tubule?
Through diffusion down its gradient
Na/H antiporter
Na/glucose symporter
How does sodium travel from the collecting duct cell to the interstitial fluid (i.e. at the basolateral membrane)?
Through an active Na/K ATPase pump
How is total body sodium sensed?
Changes in total body sodium ~ changes in extracellular fluid folume (major extracellular solute)
Sensed by baroreceptors in CV system
True/False? Plasma concentration of Soduim is an accurate marker for total body sodium
False
PNa only reflects the relative relationship of total body Na and water
How is sodium regulated in the kidneys?
Sodium excreted = sodium filtered - sodium reabsorbed
Recall Na is NOT secreted in tubules
Excretion regulated by:
GFR (minor)
Sodium reabsorption (MAJOR)
How does the GFR regulate sodium if excess sodium is lost eg due to diarrhea?
Na decreased = plasma volume decreased
= Venous pressure decreased *
= Atrial pressure decreased *
= Cardiac output decreased
= Arterial blood pressure decreased*
* have an effect on renal sympathetic nerves, constricts aferent arterioles
= Net decrease in GF pressure = decrease in GFR = decrease in Na and H2O excretion
What is the key hormone involved in sodium control via reabsorption?
Aldosteroe (steroid hormone)
Where does aldosterone stimulate the reabsorption of sodium?
DCT and CCD
Describe the Renin-angiotensin-Aldosterone System
Kidneys secrete Renin
Renin catalyzes the activation of angiotensinogen (secreted hepatically) into angiotensin I
Angiotensin I is converted by ACE into Angiotensin II
Angiotensin II acts on the adrenal cortex to secrete Aldosterone
Aldosterone promotes Na reabsorption
Which part of the kidneys secrete renin?
The juxtaglomerular cells
True/False? Aldosterone stimulates H2O reabsorption in the CCD
True/False? Aldosterone directly stimulates H2O absorption
True
False
What is ANP and how does it function?
Atrial natriuretic peptide
Secreted by cells in cardiac atria
Acts on the tubules to inhibit Na reabsorption and increases GFR
ANP is secreted when there is an increase in total body sodium
“pressure natriuresis”
Define Osmolarity, Hypoosmotic, Isoosmotic, hyperosmotic
Osmolarity: The total solute concentration of a solution
Measure of water concentration: The higher the osmolarity, the lower the concentration
Hypoosmotic: Having total solute concentration less than that of normal ECF
Isotonic: Having total solute concentration equal to that of ECF
Hypertonic: Having total solute concentration greater than that of ECF
How much water is reabsorbed?
99%
Describe the mechanism of water reabsorption in the proximal tubule
- Na+ goes down its gradient from the lumen to tubular epithelial cells
- As a result, lumenal osmolarity decreases and interstitial osmolarity increases
- To compensate, H2O travels through tight junctions AND through osmosis of epithelial cells
- Bulk flow forces H2O into peritubular capillaries
What are the two critical components to dynamic regulation of water?
The highosmolarity of the medullary interstitium
Permeability of CD to water (regulated by Vasopressin)
How is urine concentrated?
Through the countercurrent multiplier system
What does urine concentration depend on?
Hyperosmolarity of the interstitial fluid
What are the effects of vasopressin on water concentration?
In the presence of Vasopressin, water diffuses out of the ducts into the interstitial fluid in the medulla to be excreted
What are the two steps in the countercurrent multiplier system? What are the properties of each limb of Henle’s loop that make this possible?
step 1: The ascending loop of henle actively reabsorbs NaCl (osmolarity decreases)
Step 2: The descending loop of Henle detects the increased osmolarity of the interstitial fluid and releases water to compensate
Step 1 depends on the fact that the ascending loop is impermeable to water
Step 2 depends on the fact that the descending loop is permeable to water
The descending limb of Hele’s loop is ____molar compared to the ISF whereas the ascending limb is ___molar compared to the ISF
Iso
Hypo
What is the vasa recta?
The blood vessels in the medulla
Hairpin like structure, minimizes excessive loss of solute from the interstitum
Besides NaCl, what also contributes to medullary hyperosmolarity?
Urea
What would happen if instead of a vasa recta a capillary was placed running down the nephron?
The osmolar gradient would be lost
What does water reabsorption depend on? What does THAT depend on?
Water permeability of the tubules
Permeability depends on the tubular segment
eg proximal tubule has high permeability to water
eg CCD and MCD permeability is subject to physiological control (vasopressin)
What does vasopressin do? How?
Increases secretion of water in collecting duct by adding aquaporins to the LUMENAL membrane of the collecting duct cells
What is the pathological cause of Diabetes insipidus?
Malfunction in vasopressin system
What happens to the concentration of solutes (osmolarity) in the collecting duct with and without vasopressin?
With vasopressin: Concentrates as water leaves
Without vasopressin: Water stays in CD and keeps same osmolarity
How is vasopressin release regulated?
Osmoreceptor control (most important) Baroreceptor control (less important)
What is a possible reason for why we feel thirsty?
Increased plasma osmolarity
Do you lose more water or sodium when you sweat?
Water
What is the most abundant intracellular ion?
Potassium
What is the fate of ingested potassium?
90% excreted into urine, 10% excreted into feces/sweat
How do the kidneys regulate potassium?
Freely filtered at glomerulus
Normally - tubules reabsorb most of the filtered K so very little filtered K appears in urine
Unlike Sodium or water, Potassium can be _____ at cortical collecting ducts
Secreted
Changes in K excretion are due mainly to changes in K ______ in the CCD (some in DCT)
Secretion
Secretion of K in the CCD is compled with reabsorption of what ion?
Na
How is potassium secretion regulated?
Dietary intake of potassium
Aldosterone
How does Aldosterone regulate K?
Increases reabsorption of Sodium
Sodium reabsorption coupled to Potassium Secretion
Potassium secreted
When can K be excreted when it shouldn’t?
During RAAS
What happens to ion regulation during hyperaldosteronism?
Increased fluid volume, hypertension, HYPOKALEMIA, suppressed RAAS, metabolic alkalosis also observed
What is the optimal pH of the body? What concentration of Hydrogen is needed?
7.4, [H+] = 40 nanomol/L
What is the important reaction that governs Hydrogen ion balance? What happens when you lose an ion in this equation?
CO2 + H2O <=> H2CO3 <=> HCO3- + H+
When a bicarb is lost, the equation shifts to the right to compensate and a H+ is gained
What are 4 ways to gain a Hydrogen Ion, and what are the 4 opposite ways to lose a H+ ion?
- Generation of a Hydrogen ion from CO2 / Hyperventilation (loss of CO2)
- Production of nonvolatile acids from metabolism of proteins / utilization of hydrogen ions in the metabolism of various organic anions
- Gain of H+ due to loss of bicarb in diarrhea/ Loss of Hydrogen ions in vomitus
- Gain of hydrogen ions due to loss of bicarb in urine / Loss of hydrogen ions in urine
Name 3 nonvolatile acids
Phosphoric acid
Sulfuric Acid
Lactic acid
What is a buffer solution?
Any substance that can reversibly bind hydrogen ions
Most hydrogen ions are buffered by extracellular and intracellular buffers
Buffer- + H+ <=> HBuffer
True/False? Buffering eliminates hydrogen ions from the body
False (it only keeps them locked up)
What is the ultimate balance of hydrogen ions controlled by?
Respiratory system (by controlling CO2) Kidneys (by controlling HCO3-)
How do the kidneys control H+ ions?
By controlling excretion/production of HCO3-
Low H+ conc (alkalosis): Kidneys excrete HCO3-
High H+ conc (acidosis): Kidneys produce HCO3-
What is the Henderson-Hasselbach equation?
pH = 6.1 + log([HCO3-]/[CO2])
pH = -log(Ka) + log([HCO3-]/0.03[CO2])
where Ka is the dissociation constant for CO2/HCO3- system
0.03 is solubility of CO2 at 37 C
How do the kidneys handle HCO3-?
H2O and CO2 combine in tubular epithelial cells to form H2CO3 which dissociates into H+ and HCO3-
H+ is secreted into tubular lumen where it combines with a filtered bicarb and forms H2CO3 which reforms H2O and CO2
HCO3- enters ISF
Where does most HCO3- reabsorption occur?
In the proximal tubule
How is a new HCO3- added to the plasma?
Either by excreting a H+ (using nonbicarbonate buffers such as phosphate)
or by glutamine metabolism with NH4+ secretion
Botth processes are considered to be H+ excretion (which shifts the reaction to produce more bicarb)
How do the kidneys add a new HCO3- to the plasma using Phosphate?
H2O and CO2 combine in tubular epithelial cells to produce H2CO3 which dissociates into H+ and HCO3-
The H+ is ACTIVELY pumped into lumen where it binds to filtered phosphate forming phosphoric acid which is then excreted
The HCO3- is then released into the ISF
- This only happens after all the HCO3- has been reabsorbed and is no longer available from the lumen
How do the kidneys add a new HCO3- to the plasma using glutamine?
Glutamine enters the tubular epithelial cells with Na+
Glutamine is broken down into NH4+ and HCO3-
NH4+ enters tubular lumen using a sodium antiporter (Na+ enters epithelial cell) and the NH4+ is excreted
The HCO3- is then released itno the ISF
- mianly occurs in proximal tubule, this is called “H+ ecretion bound to NH3”
During respiratory acidosis, what happens to H+ levels? HCO3- levels? CO2 levels?
What causes the HCO3- change? What causes the CO2 change?
What about alkalosis?
H+: inc
HCO3-: inc (renal compensation)
CO2: inc (primary abnormality)
reverse for alkalosis
During metabolic acidosis, what happens to H+ levels? HCO3- levels? CO2 levels?
What causes the HCO3- change? What causes the CO2 change?
What about alkalosis?
H+: inc
HCO3-: dec (primary abnormality)
CO2: dec (reflex ventilatory compensation)
reverse for alkalosis
What are the renal responses to acidosis? what is the net result?
High H+ conc
Sufficient H+ are secreted to reabsorb all filtered HCO3-
Still more H+ are secreted and this contributes new HCO3- to the plasma as these H+ are excreted bound to non-HCO3- buffer (eg HPO4–)
Tubular glutamine metabolism and ammonium excretion are enhanced, which also contributes new HCO3- to plasma
Net result: more HCO3- than usual added to plasma, compensating for acidosis (urine is acidic)
What are the renal responses to alkalosis? What is the net result?
(low H+ concentration)
Rate of H+ secretion is inadequate to reabsorb all filtered HCO3-, so HCO3- is excreted in urine
Little or no H+ secretion on non-HCO3- buffers
Tubular glutamine metabolism and ammonium excretion are decreased so that little/no new HCO3- is contributed to plasma
Net result: Plasma HCO3- will decrease, thereby compensating for alkalosis (urine is alkaline)
How do diuretics function?
Act on tubules to inhibit the reabsorption of sodium along with chloride and/or bicarb, resulting in increased excretion of these ions (water excretion rises too)
Where does a loop diuretic act ? how?
Acts on thick ascending limb of loop of henle
Inhibits cotransport of Na, Cl and K
eg furosemide, most commonly used diuretic
Where does a potassium-sparing diuretic act/ how?
Inhibits Na reabsorption in the CCD, and therefore inhibits K secretion there
Thus, unlike other diuretics, plasma [K] stays the same
Blocks action of aldosterone or blocks the (ald-regulated) epithelial Na channel in CCD
eg amiloride
When would you use diuretics? name two cases
Congestive heart failure (lower CO)
Hypertension (retention of salt and water causes high BP)
What are common features of kidney disease/failure?
Proteinuria Accumulation of waste products in blood High [K] in blood Metabolic acidosis Anemia Decreased Vitamin D (leading to hypocalcemia)
When do Kidneys fail?
When more than 90% of nephrons stop working (Fatal)
What are three methods of renal replacement therapy?
Hemodialysis
Peritoneal dialysis
Kidney transplantation
What is hemodialysis
A machine filters your blood "arterial blood" goes through pump given anticoagulant dialysis fluid drained off Dialyzer removes waste products Dialysis fluid input (concentrate and purified water) Airtrap and air detector "venous" blood returned to patient
What is peritoneal dialysis?
The lining of the patien’ts abdominal cavity is used as a dialysis membrane
Fluid is injected into the cavity, solutes diffuse into the fluid from the person’s blood, and the fluid is exchanged several times a day
WHat is a kidney tranplantation?
Either from a recently deceased person of from a living relative/or immunosimilar donor
Antirejection treatments have improved over the years (organ shortage is nor a problem)
Donors can funciton with just one kidney
