Chapter 7 (exam 2)

Question 1

Kidney Functions

Answer 1

• reg blood volume and pressure
• ion concentrations
• regulate pH
• conserve nutrients and eliminate waste/tox
• metabolism of drugs/tox
• filtrations (180L per day)

Question 2

Bowman’s Capsule

Answer 2

• glomrulus inside with fenestrated capillaries
• pores in capillary allow small parts to enter the kidney
• Albumin, blood cells fo not enter the nephron

Question 3

Proximal Convoluted Tubule

Answer 3

• Retains nutrients (amino acids and glucose) and water
• active transport to help retain nutrients
• Pump Na⁺ out and water will follow due to osmosis (passive)
• some enzymes pull in Na⁺ while removing glucose (antiporter)

Question 4

Loop of Henle

Answer 4

• ion regulation and water reabsorption
• osmolarity increases in descending limb as water is removed
• remove salt in ascending limb and decrease osmolarity
• bottom is highly stressed due to high conc
• countercurrent with vasa recta blood vessel, more efficient than static system

Question 5

Osmolarity

Answer 5

mole solute/L solution

osmosis - diffusion of water across membrane

increases in descending limb and decreases in ascending limb

Question 6

Collecting duct

Answer 6

• water balance
• after PCT

Question 7

Renal susceptability to Tox

Answer 7

• highly perfused - 20-25% cardiac output
• high solute conc
• active transport
• bioactivation due to metabolic activity

Question 8

Kidney injuries

Answer 8

hypofiltration - decrease rate of filtration due to renal vasocconstriction or glomerular injury (amphotericin B increases permeability, loss gradient)

tubular necrosis - wide variety of chemicals that can cause widespread cell damage

obstruction - loss of flow (radiocontrast agents form precipitate due to high conc in tubular fluid)

fibrosis - immune, inflammatory effect

Question 9

Measurement of GFR

Answer 9

• glomerular flow rate
• use serum creatine and urea (blood urea nitrogen, BUN) concentrations as biomarker
• Constantly generated throughout the body

readily eliminated by the kidney. Increase conc corresponds to decrease in filtration rate

-mass balance (in-out)

Question 10

Urinalyasis

Answer 10

Chemical analysis of solute conc and pH

-proteinuria - protein in the urine (albumin)

–due to injury to the glomerulus via high blood pressure

Question 11

Ethanol Renal Impact

Answer 11

• inhibit ADH
• less ADH results in less water reabsorption in the collecting duct
• less conc urine, higher volume, dehydration
• ADH promotes water retention via collecting duct

Question 12

Chlorinated Solvents (Renal)

Answer 12

• TCE - trichloroethylene
• GSH generates reactive metabolites
• beta-lyase cleaves the cysteine off of the (-SG) conjagate to form a nucleophile
• nucleophile is highly reactive and forms an adduct

Question 13

Metal Renal Tox

Answer 13

• Cd and Hg (non-nutrative metals)
• Negative effects because of sulfur chemistry
• transition metals (soft metals, more polarizable) have high affinity for reduced sulfur
• soft metal has high affinity for soft ligands (O is hard, S is soft)
• soft metals in bottom right of periodic table

Question 14

Bio source of Reduced Sulfur

Answer 14

• thiols in proteins, GSH (gluothione conjugation)
• metal binds to thiol on protein and alters the tertiary sructure
• loss of function for active transporters required for kidney function

Question 15

Metallothioneins

Answer 15

• cysteine rich proteins that are used to sequetser nutrient metals like Zn or that serve as non-essential target for toxic metals (Cd)
• Produced in liver and kidneys
• Inducible and chronic exposure can increase production therefore it is a biomarker for exposure

-

Question 16

Metallthioneins mechanism

Answer 16

• metal binds to MTin liver instead of an essential protein
• metal-MT complex is excreted in urine thorugh the kidney (its small)
• Cd-MT is reabsorbed in the PCT

–looks like a protein that should be conserved and recycled

• PCT cell recycles via the lysosome (release Cd²⁺)
• Free Cd²⁺ binds to essential proteins (degrade cell function) or MT in the PCT cell
• MT supply depleted

Question 17

Pb in the Kidney

Answer 17

• reabsorbed in the PCT
• binds to sites in mitochondria, decrease energy
• decrease active transport of essential nutrients being reabsorbed
• Cisplatin(chemotherapy drug) also binds to mitochondria and inhibits electron transport and generates ROS
• ROS can alter structure of essential bio molecules

Question 18

Mercury in Kidney

Answer 18

50% of dose can be found in the kidney in a few hours

• PCT necrosis in 24-48 hrs after acute exposure
• PCT reabsorption decreases and damage to mitochondria

Question 19

Metal Tox in Aquatic system

Answer 19

• related to impacts on gills
• gill functions - respiration (dissolved gas exchange), ion regulation (osmoregulation), similar to mammal kidney
• freshwater-uncontrolled lose ions
• salt water - uncontrolled gain ions or lose water
• brackish water - isoosmotic
• Ca²⁺, Na⁺, K⁺, Mg²⁺ other ions are trace

Question 20

Biotic Ligands (fish gills)

Answer 20

• metals target the biotic ligands (lone pairs, negative charges)
• ion transport protein
• Binding affinity series NA<k></k>

<p>-trace ions preferably bind to the ion transport protein</p>

<p>--longer residence time</p>

<p>--inhibit normal ion balance</p>

<p>--lose osmotic balance</p>

<p> </p>

</k>

Question 21

Biotic Ligand Model

Answer 21

Zn + Ca-BL equil Zn-BL +Ca

Zn + BL equil Zn-BL K_f

also Zn + Cl equil ZnCl

Competition between trace metals and major ions for the biotic ligand

• betwen other ligands and metal ions
• increase in major ion concentration will decrease tox because ion will be more competitive than metal
• site specific water quality criteria is based on BLM

Question 22

Dissolved Organic Matter

Answer 22

• decay products from platn material, large MW, wide array of sizes and structures
• contain functional groups that can be ligands