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135 Cards in this Set

  • Front
  • Back

What are the functions of the kidney?

-regulate water, electrolytes, blood pressure and acid-base balance


-metabolism of endogenous and exogenous compounds


-excretion of chemicals, waster products


-endocrine functions

Define xenobiotic

a foreign chemical substance that is NOT normally/naturally produced or expected to be present within an organism

Define nephrology

the study of normal kidney function, kidney problems, the treatment of kidney problems, and renal replacement therapy

Define Urology

focuses on the surgical and medical diseases of the male and female urinary tract system and the male repro.

What are the 3 main sections of a kidney?

The cortex, inner medulla, and outer medulla

What is the functional unit of the kidney?

the nephron

What makes up the nephron?

vessels into the glomerulus, the glomerulus, PCT, DCT, loop of Henle, and the collecting tubules

What is the relationship between animal size and the number of nephrons?

As the animal gets bigger, they have more nephrons.


ex: cow has 4 million, cat has 200,000

What makes up the proximal tubule?

the proximal convoluted tubule and the Pars Recta

What part of the nephron has a brush border?

the proximal tubule

What part of the nephron has a lot of metabolic activity and why?

the proximal tubule to help transport substances across the cell membrane from the lumen of the tubule.

What are the segments to the loop of Henle?

thin descending, thin ascending, thick ascending (in this order)

What are the segments of the distal convoluted tubule?

early and late segments

What are the segments of the collecting tubules?

cortical, outer medullary, and inner medullary

Formula for Urinary Excretion

Urinary Excretion= Filtered load + tubular processing

Urinary Excretion= Filtered load + tubular processing

What is the renal clearance formula?

What is the "gold standard" substance used to measure for glomerular filtration rate (GFR)? why?

Inulin. It is NOT secreted or absorbed just filtered in the kidney.

What should the clearance of Albumin be?

close to zero. Plasma proteins should NOT make it into the urine unless there is a major problem.

What is PAH clearance measurements used to determine?

Renal plasma flow (RPF) because it is filtered and secreted.

How can you tell if a substance was secreted or absorbed in the kidney?

You compare it to the clearance of inulin.


(clearance of substance/C of inulin)


-If it=1, there is no net secretion or reabsorption


-If it is >1, net secretion


-<1, net reabsorption

Where is most of the blood flow to the kidney going?

to the cortex (about 93%)


-6% to the outer medulla


-1% to the inner medulla

What type of arteriole delivers blood to the glomerulus?

the afferent arteriole

What type of arteriole takes blood away from the glomerulus?

the efferent arteriole

What happens to blood flow when alpha-1 receptors are stimulated?

-vasoconstriction by releasing NE


-decreases renal blood flow and glomerular flow rate

What are more alpha-1 receptors located: efferent or afferent arterioles?

afferent arterioles

What happens at low levels of Angiotensin II?

glomerular flow rate will increase because you are mostly causing vasoconstriction in the efferent arterioles

What happens at high levels of Angiotensin II?

Glomerular flow rate will decrease because it is then affecting the afferent arterioles as well.

What are the effects of Atrial Natriuretic Peptide on the kidney?

-dilate afferent arterioles


-constricts efferent arterioles


-Net decrease in vascular resistance


-Increases renal blood flow and GFR

What vasodilator is produced by the kidney in response to increased Angiotensin II and Catecholamine levels?

Prostaglandins (E2 and I1) as a protective response

What is the effect of prostaglandins on the kidney?

-vasodilation of efferent and afferent arterioles


-increases RBF

What drugs inhibit the protective vasodilation activity of Prostaglandins?

NSAIDS

What is autoregulation?

It means the kidney is able to maintain a stable RBF at a range of different pressures


-ANS is NOT involved in this


-relies on renal resistance

Below what renal artery pressure do we see a decrease in Renal blood flow?

below 80 mmHg

Describe the Myogenic Autoregulation Theory

As pressure in the kidney goes up, there is a stretch blood vessel detects it and constriction reflex occurs.


-Stretch opens up Ca2+ channels that increases smooth muscle contraction leading to more resistance in the blood vessels.

Describe the Tubulo-Glomerulo feedback theory of kidney autoregulation

As GFR increases, so does solute delivery to the Macula densa. This is senses causes vasoconstrictors to be released.


-Vasoconstrictors cause constriction of afferent arterioles through autocrine system.


-prevents excessive loss of solute

What substance is measure to determine renal plasma flow (RPF)? Why?

Para-Aminohippuric Acid (PAH) because it is filtered and secreted but does NOT alter RPF

Describe the main idea behind the Fick principle?

The amount of PAH going into the renal artery has to equal the amount that is coming out (either through renal vein or urine)

Formula for RPF

RPF= ([urine PAH times V)/[P PAH]

How do you convert renal plasma flow to renal blood flow?

RBF= RPF/(1-hematocrit)

What happens to renal blood flow as hematocrit increases?

It increases as well.

What is the first step in producing urine?

glomerular filtration

What is glomerular ultrafiltrate similar to?

plasma except ultrafiltrate does not have proteins in it

What are the layers to the glomerular capillary and what is contained in each?

1. Endothelium with pores


2. Basement membrane with lamina interna, lamina densa, and lamina externa


3. Epithelium with podocytes, foot processes, and filtration slits

What is the main mechanism to keep proteins from being filtered through the glomerulus?

The glomerulus has a fixed negative charge. this stops larger negative charged things (like proteins) from crossing its membranes

Rank negatively charged, positively charge, and neutral things by how easily they are filtered through the glomerular membrane.

Negatively charged (hardest time), neutral, positively charged (easiest time)

What happens to filtration when oncotic pressure increases?

Filtration goes down.


What happens to oncotic pressure as you get closer to the end of the glomerulus?

It increases.


--Water is leaving the glomerulus but proteins are not so their concentration is going up and up

What is the net filtration at the end of the glomerulus? Why?

It is zero because the oncotic pressure keeps rising. This is causing water to reenter the glomerular capillary instead of being filtered out.

Describe the effects of an increase of SNS or high levels of Angiotensin II on the GFR and RPF

Decrease GFR and RPF.


EX: increase in SNS and high levels of AG-II

Describe the effects of constricting efferent arterioles on GFR and RPF.

decrease RPF but increase GFR


Ex: low levels of AG-II

What are the requirements for a marker that best measures GFR?

-need something that is filtered but not secreted or absorbed


-should not be handled at all by the tubules


-little protein binding


-does not alter GFR itself


-good size/charge to be freely filtered across the glomerulus

What is the ideal substance used to measure GFR?

Inulin

Formula for GFR of Inulin

GFR= ([urine inulin]/[plasma inulin] times urine flow rate

Why do we measure GFR?

it is a measure of the functional renal mass.


-Are kidney's healthy or not?


-Changes way before blood levels change to indicate a problem

Define Filtration fraction

GFR divided by RPF


-used more in research than in clinics

What does the filtration fraction show?

How much blood is taken out in the glomerulus (answer to fraction)


-remaining blood is going to the peritubular capillaries

What is an easier way to measure GFR than collecting urine?

Iohexol can be injected and tested in the serum at 1,2 and 3 hours. Iohexol is ONLY filtered by the kidneys so its concentration in serum shows how quickly the kidneys are filtering it out.

What happens to serum creatinine levels in the blood as GFR (function nephrons) goes from 100% to 50%

NOTHING

What percentage of the kidney nephrons are still functional when serum Creatinine levels start to change?

25%


After this point, creatinine levels change very quickly

Where does s-Creatinine come from?

the muscles.


It is a product of phophocreatine break down


-produced at a constant rate

How is BUN produced in the body?

It is the end product of protein and AA break down.


-not produced at a constant rate

What is s-creatinine a better measure of GFR than BUN?

BUN is NOT produced at a constant rate. It varies on the diet, when you ate last etc.


Creatinine is produced at a constant rate

When you get high levels of BUN or s-creatinine in a blood work up, what should you be worried about?

kidney function or GFR

What are some advantages to testing SDMA instead of Creatinine to detect kidney function?

-It changes earlier (at about 25% kidney loss)


-It is only filtered by the kidney like s-creatinine


-it does not appear to be affected by animals muscle mass

How are s-creatinine levels altered by muscle mass?

When an animal loses muscle mass, creatinine levels go down. This means s-creatinine could show at a normal level even though the animal has a kidney problem.

What is most renal work related to?

Na+ reabsorption

Formula to determine if something is secreted or absorbed

Filtered load-excretion rate


0= no net tubular effect


+ = reabsorbed


- = secreted

What is usually also reabsorbed with sodium in the kidney?

glucose through secondary active cotransport

How is Na+ usually pumped out of the cell into the blood?

Na+/K+ ATPase

What is the renal threshold?

The blood sugar level when glucose starts showing up in the urine


-around 200 mg/dL

What is T max?

the max number of mG of glucose the tubules are capable of reabsorbing


-all glucose carriers are saturated

What is tubular splay?

the different between the threshold and the T max


-caused by some low affinity transporters that allow glucose to attach/detach, attach/detach

What is occurring during hyperglycemia?

the amount of glucose has exceed the renal threshold and glucose is seen in the urine


-Ex of causes: diabetes mellitus and stress

What can occur to glucose transport during pregnancy?

During pregnancy, GFR is increased. This increases the filtered load of glucose. The higher load of glucose exceeds transporter capacity.

Where is glucose primarily reaborbed at in the kidneys?

proximal tubules

Describe urea handling in the kidney.

-filtered and reabsorbed. can be secreted


-free flowing


-generally follows water reabsorption (same direction)

Where are urea concentrations usually the highest in the nephron? Why?

in the thick ascending limb and distal convoluted tubule because it can not follow water movement in these areas.


-water can get out but urea canNOT

What parts of the nephron are NOT permeable to urea?

ascending loop, DCT, Cortical convoluted collecting tubule, outer medullary collecting tubule

Define isosmotic reabsorption

Water went along in the same proportion as the substance so the concentration remains the same

What part of the nephron contributes to most of the Na+ reabsorption?

the proximal convoluted tubule (67%) and the thick ascending limb (25%)

How are Na+ and H2O reabsorption linked in the proximal tubule?

-water follows the movement of Na+


-They are reabsorbed in proportion (isosmotic reabsorption)

What is the key transporter that favors the movement of Na+ into the cell across a permeable membrane?

The Na+/K+ ATPase moves Na+ keeps a low concentration of Na+ in the cell (moves it into the blood) so Na+ wants to cross the permeable membrane from the lumen

What cotransporter is predominantly used to reabsorb Na+ in the early proximal tubule?

with HCO3-

By the late proximal tubule, what ion is left to be absorbed?

Chloride.


-Glucose, AAs and HCO3 have all been reabsorbed by now.

What cotransporter is used with Na+ reabsorption in the late proximal tubule?

Chloride

What would you expect to happen to tubular reabsorption if GFR goes up?

It would increase too.

What happens to the reabsorption of water and solutes when you give IV fluids? (explain in detail)

-Reabsorption decreases because the fluids dilute the protein concentration (oncotic pressure) and increase the pressure in the capillaries. Expanding the Extracellular fluid volume These conditions do NOT favor solute/water movement into the capillaries

What type of permeability occurs in the thin ascending and thin descending loops of Henle?

Passive permeability...little to no energy is being used

Describe the cellular mechanism for Na+ reabsorption in the thick ascending limb of the loop of Henle.

-3 ion transport system


-1 Na+, 2 Cl-, and 1 K+ must bind for transporter to work.


-Cl- and K+ diffuse into blood down concentration gradient


-Na+ uses Na+/K+ ATPase to get into blood

What hormone enhances the function of the Na+K+Cl- cotransporter in the thick ascending limb?

ADH (antidiuretic hormone)

What part of the loop of Henle is NOT permeable to water?

the entire ascending limb (thin and thick portions) and the early distal tubule

Describe the diluting segment of the nephron

-from the hair pin turn to the distal convoluted tubule


-Na+ is able to enter the cell from the tubule lumen but water canNOT


-this causes dilution of the urine because ion concentration decreases

Where is the first location for a Na+/Cl- transporter in the nephron?

the early distal convoluted tubule


What group of drugs can block the Na+/Cl- transporter?

Thiazide diuretics (used in heart failure patients to get more Na+ out of the body)

How does Na+ enter the cell from the lumen in the late distal tubule and collecting ducts?

Through an electrical channel


-NO cotransporters in the principal cells here

What happens to K+ in the late distal tubules?

It is favored to leave the cell and enter the urine.

Describe the function of Aldosterone. Where does its action occur?

It increases the number of Na+ channels in the late distal tubule so that more Na+ can be reabsorbed.


This also increases the transport of K+ out of the cell into the urine

Describe the function of principal cells in the late distal tubule

Favor Na+ reabsorption, K+ secretion and are permeable to water if Aldosterone is present

What is the function of the alpha-intercalated cells in the late distule tubule?

K+ reabsorption and H+ secretion

What is the effect of ADH on the late distal tubule?

It changes the permeability of water in this location

What drugs can be used to inhibit the effect of Aldosterone in the late distal tubule?

K+ sparing diuretics (triamterene, amiloride, and spironolactone)


-used to increase Na+ secretion

What is going to happen in the kidney if the animal increases Na+ intake?

-increase in ECF and EABV


-Decrease in SNS (dilate afferent arterioles to increase GFR)


-Increase ANP


-Decrease osmotic pressure and aldosterone


-NET EFFECT: increase Na+ excretion


What is going to happen in the kidney if the animal decreases its Na+ intake?

-NET EFFECT: increase Na+ reabsorption


-Increase SNS (vasoconstriction)


-decrease ANP


-increase osmotic pressure and Aldosterone

Where is most of the K+ in the body located at?

inside cells (98%)

What can insulin cause in terms of K+? How?

Hypokalemia (K+ deficiency) by increasing Na+/K+ ATPase. It can cause more K+ to be pushed in to cell

What are some things that cause K+ to leave cells?

-extreme dehydration (K+ flows with H2O out of the cell


-exercise


-cell lysis


-metabolic acidosis: H+ going into the cell pushes K+ out

Where is most of K+ reabsorbed at?

the proximal tubule (67%) and the thick ascending limb (20%)

What is unique about K+ secretion?

It varies greatly. It can be 1% or up to 110% depending on your dietary amounts of K+ and the body's need for it

What brings K+ into the cell in the thick ascending limb?

The 3 ion (Na+/Cl-/K+ cotransporter) transporter

What drug can cause hypokalemia by disrupting the 3 ion transporter in the thick ascending limb?

Furosemide (Lasiks) or diuretics

Where does the fine tuning of K+ levels occur in the nephron?

the late distal tubule and collecting ducts

Describe what happens to K+ in alpha-intercalated cells of the late distal tubules?

K+ and H+ are pumped in from the lumen using ATP (primary active transport)


K+ is pumped out of the cell through Na+/K+ ATPase and a K+ ion channel

Describe what happens to K+ in the principal cells of the late distal tubules

Na+ comes in through an electrical channel and K+ is secreted into the lumen through an electrical channel

What is the main determining factor on how much K+ is reabsorbed or secreted?

the concentration of K+ inside the cells (size of the electrochemical gradient)

What is aldosterone's effect on Na+ reabsorption?

It increases K+ secretion by principal cells by causing insertion of K+ channels in the luminal membrane

What happens to K+ if the animal has acidosis?

H+ ions are going to be pushed out of the cells into the urine. This will decrease K+ secretion.

What happens to K+ if an animal is alkalotic?

K+ secretion will be increased. H+ ions will be pushed into the cells which pushes K+ out of the cells

Explain how Loop diuretics and thiazides increase K+ secretion.

They block Na+ reabsorption upstream. This causes more Na+ to be delivered to the principal cells of the distal tubules. These cells will secrete more K+ so they can absorb more Na+.


They also increase flow rate which dilutes K+ causing more to be lost

What is the group of hormones that help regulate phosphate homeostasis?

Phosphatonins. Tend to lower Phosphorous in the body

Where is most phosphorous reabsorbed at?

the proximal tubule

What is there such a high amount of phosphorous in the urine?

It acts as a buffer for acid secretion.


15% is excreted

What is the only substance that is "fine tuned" in the proximal tubule?

phosphorous

Describe PTH's affect on Phosphorous reabsorption.

It blocks the Na+ phosphate luminal cotransporter in the PCT by making it internalized ("hiding it"). This causes excess Phosphorous in the urine (a.k.a. phosphaturia)

What is the most important phosphatonin?

Fibroblast Growth Factor 23 (FGF-23)

What are the effects of FGF-23?

It decreases activity of Na+/phosphate cotransporter in the PT and decreases the production of calcitriol.


Overall, increases Phosphorous in the urine and decreases phosphorous absorption in the SI

What is ultrafilterable calcium?

It is the calcium that CAN go through the glomerulus. It contains the complexed to anions and ionized forms. (do not include protein-bound calcium)

What happens to ionized Ca2+ levels during acidemia? Why?

Ionized Ca2+ levels increase.


This is because more H+ ions bind to albumin and less Ca2+ are able to bind.

What is PTH's effect on Ca2+ reabsorption? Where does this happen?

It increases Ca2+ reabsorption in the late distal tubule

Why is Calcium reabsorbed in the mTAL?

because the lumen becomes charged due to Ma+/Cl-/K+ pump. This drives some positive ions (like Calcium) into paracellularly into the blood

What ions are lost due to loop diuretic drugs?

Na+, K+, Cl- and Calcium

What is the only location in the nephron where Calcium absorption is NOT paired with Na+ absorption?

the distal convoluted tubule

Why would you give thiazide diuretics to a patient with chronic urinary calcium stones?

They increase Ca2+ reabsorption and decrease excretion in the urine.

What is the protective protein that transports Ca2+ across the cell?

Calbindin

Where is the major site of Magnesium reabsorption in the nephron?

the medullary thick ascending limb

What drives Magnesium reabsorption in the mTAL?

a positive charge in the lumen from the 3 ion cotransporter drives Magnesium paracellularly