SWG Renal Exam 1: Intro to Renal Physiology (Part 1) (P900/IC)

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What is the clearance of inulin, and why?

180 mL/min, because inulin is ONLY FILTERED and NOT reabsorbed or secreted!! So the clearance rate = GFR note: from notes beneath slide 32

The kidneys receive approximately what percentage of cardiac output? Also, approximately what percentage of blood volume is lost (filtered) across the glomerular capillary endothelium?

20-25%; 20%

Which part of the kidney's gross anatomical structure receives the most blood?

>80% of all blood to the kidneys is in the renal CORTEX!

If the quantity excreted is more than the quantity filtered, then you know there was a net (reabsorption/secretion) of the solute while passing through the renal tubules

Net SECRETION!

What are the key take-away points regarding glomerular filtration? *High yield!*

"For most ions and small organic molecules (ie glucose, amino acids, etc), the concentration in the filtrate entering the proximal tubule is *identical* to that of the plasma. For some solutes (solutes that bind to proteins, some small to medium sized proteins), the concentration in the filtrate entering the proximal tubule is *less than* that of the plasma. This includes divalent cations, like calcium, and lipophilic hormones (e.g., steroid hormones, thyroid hormone) that are bound to "carrier" proteins in the plasma."

TEST: If very little filtrate is actually excreted, how does urine volume vary?

"the *excretion fraction* (and thus *volume excreted*) is under hormonal control and *does vary* based on the volume of fluid ingested and how much is lost via extra-renal sources (sweat, water vapor in breath, vomiting/diarrhea)"

In renal physiology, concentration of a given solute in filtrate is equal to what?

(QUANTITY of a solute in filtrate) / (volume of filtrate)

What is the clearance of glucose, and why?

0 mL/min,m because all the filtered glucose is REABSORBED!! note: from notes beneath slide 32

TEST: How do you calculate the percentage of plasma in whole blood?

1 - hematocrit, expressed as a percentage Recall: hematocrit is the portion of the blood that contians all the various cells, while the rest of it is plasma

What are the three major subdivisions of the collecting duct?

1) Cortical collecting duct (CCD) 2) Outer medullary collecting duct (OMCD) 3) Inner medullary collecting duct (IMCD)

What are the 3 major functions of the kidney?

1) Excretion of metabolic wastes/bioactive molecules *2) Water and electrolyte homeostasis* - regulation of arterial BP, pH homeostasis 3) Production/activation of hormones and other molecules - erythropoietin, calcitriol, gluconeogenesis

TEST: What are the 4 basic major renal processes?

1) Filtration at the glomerulus 2) Reabsorption 3) Secretion 4) Excretion

GFR is primarily influenced by what two factors?

1) Filtration coefficient *2) Net filtration PRESSURE*

What are the two main criteria for a solute to be freely filtered by the glomerulus? What are some examples?

1) Must be SMALL enough to readily move through filtration barriers 2) Must NOT be PROTEIN-BOUND Examples: Univalent electrolytes (Na, K), glucose, amino acids

The efferent arteriole dumps blood into what two capillary beds?

1) Peritubular capillaries (CORTICAL cap bed) 2) Vasa Recta (MEDULLARY cap bed)

Secretion of solutes into renal tubules can either be one of what two ways?

1) Transepithelial (solute must cross both basolateral and apical membranes) 2) Cellular (solute is made inside epithelial cell, only needs to cross apical membranes)

TEST: The higher the plasma creatinine concentration, the (higher/lower) the GFR

The LOWER the GFR (makes sense, if creatinine is higher in the plasma, it isn't in the filtrate!)

TEST: What is the equation to calculate clearance rate? Does this equation look familiar?

C = (U x V) / P This equation is the exact same as the one used to ESTIMATE GFR, assuming the solute isn't reabsorbed or secreted within the nephron.

The clearance rate is used to compare which two rates?

Compares the rate at which the glomeruli FILTER a substance with the rate at which the kidneys EXCRETE it into the urine

The DCT begins at/just after the ______ ______, and the last segment that joins the nephron to the collecting duct is often subdivided into what TWO parts?

DCT begins at/just after the MACULA DENSA, and the last segment that joins the nephron to the collecting duct is subdivided into: 1) Connecting tubule (CNT) 2) Initial Collecting Tubule (ICT)

The renal medulla contains what parts of the nephron?

Loop of Henle, medullary collecting duct

TRUE or FALSE: The processes of filtering, reabsorbing, and secreting into/from the renal tubules are the only ways to change the quantity of a solute in the lumen of a nephron

FALSE! Solutes can be SYNTHESIZED by molecular precursors within the lumen, or solutes can be CATABOLIZED in the lumen (thus forming a new solute)

TEST: What is the equation to calculate filtration fraction (FF)? What does it represent? List how to calculate any variables used.

FF = GFR / Renal plasma flow - This represents the % of PLASMA volume that was filtered across the glomerular capillaries Renal plasma flow, or RPF = renal blood flow x percentage of plasma in whole blood

TEST: How do you calculate the quantity of a solute that is EXCRETED without knowing the concentration in the urine?

Filtered load (quantity of solute in filtered) - quantity of solute reabsorbed + quantity of solute secreted F - R + S = E Makes sense! Take how much solute is actually put into the filtrate, subtract how much is removed from reabsorption, and add in how much is secreted into filtrate = how much solute is actually excreted in urine!

TEST: What is the definition of filtered load, and how do you calculate it?

Filtered load = Amount (mass QUANTITY) of some solute that is filtered across all the glomeruli per UNIT TIME (Quantity/time) for a solute that is freely filtered: *filtered load = plasma concentration (of given solute) x GFR*

AGAIN: Filtered load is calculated by multiplying _____ by ______ concentration of a given solute. This means that the solute must not be ______ or ______ in the nephron.

Filtered load = GFR x Plasma concentration This means the solute in the plasma must not be SYNTHESIZED or DEGRADED in the nephron

How does blood flow through the kidneys? Of note, what makes the renal capillary system unique?

From the renal aa., blood eventually flows through the *afferent arteriole* into the *glomerular capillary network*. However, UNLIKE other parts of the body, blood moves from the capillaries into a second set of arterioles (*efferent arterioles*), then into the *peritubular capillaries and vasa recta* before reaching the venous system. (Note: The vasa recta are peritubular capillaries too, just the ones around the loops of Henle)

TEST: What is the equation to calculate GFR? This equation only holds true if there is what condition?

GFR = (U x V) / P Condition: There is NO further reabsorption or secretion of the solute once it is filtered!!!! Essentially, this equation results if you set FILTERED LOAD (P x GFR) = QUANTITY OF SOLUTE EXCRETED (V x U) **** There are only a few solutes that fall under this category, such as INULIN and CREATININE

TEST: Define glomerular filtration rate (GFR). It measures the efficiency of what?

GFR = VOLUME of fluid filtered into all Bowman's capsules of BOTH kidneys per UNIT TIME Measures the efficiency of your kidney's ability to FILTER

What is the GFR per minute and per day? How much plasma volume is in our blood? What does this imply about the filtration and reabsorption process?

GFR: - 125 mL / min - 180 L / day If the plasma volume is only 5 L and 180 L of fluid is filtered per day, that means the enter plasma volume is filtered (on average) 36x (not 80, that would be 400L) per day! It also implies that almost all the fluid that is filtered must be reabsorbed (or you would be constantly drinking huge volumes of liquid every day!).

When does the filtered load = quantity of solute excreted?

If there was no NET reabsorption or secretion!

The renal medulla has very low blood flow through what structure?

LOW blood flow through the VASA RECTA

TEST: What is the role of the Loop of Henle?

LoH continues to reabsorb NaCl and WATER and participates in producing conditions that allow for a CONCENTRATED or DILUTE urine

AGAIN: The loop of Henle is predominantly a (cortical/medullary) structure

MEDULLARY

The renal cortex contains what parts of the nephron?

PCT, DCT, connecting tubule, and cortical collecting duct

What lab value is a good indicator of GFR and subsequently kidney health?

Plasma creatinine

What part of the nephron is the longest section?

Proximal convoluted tubule (PCT)

TEST: What is the role of the proximal convoluted tubule?

Reabsorbs most of the filtered: - Water - NaCl - NaHCO3 Reabsorbed essentially ALL of the: - Organic nutrients

TEST: What is the MAIN function of the nephron?

Recover most of the solutes and water filtered at the glomerulus

Glomerulus and Bowman's capsule together make up what?

Renal corpuscle

What is secretion? In general, solutes that are secreted into the renal tubules (are/are not) reabsorbed.

Secretion is the process of transporting solutes *into the lumen of the nephron*; solutes Are NOT reabsorbed after secretion, they end up being EXCRETED in the urine

TEST/AGAIN: Compare the composition of blood plasma and glomerular filtrate

Similar compositions in terms of most inorganic ions and low MW organic solutes, but the PROTEIN concentration in the filtrate is LOW as proteins are not freely filtered!! Also, the filtrate has NO BLOOD CELLS

TEST: What is the difference in composition between blood plasma and glomerular filtrate?

Similar, except blood plasma has a HIGH PROTEIN content (since proteins aren't freely filtered through the glomerulus)

TEST: How do the filtration forces differ in the glomerular capillary bed compared to most other systemic capillary beds?

Since the glomerular capillaries are relatively close to the aorta, there is enough blood pressure to favor a net filtration OUT into Bowman's space over the ENTIRE LENGTH of the capillary bed. (even overcoming the osmotic inward reabsorption pressures) Most systemic capillary beds tend to favor net filtration near the ARTERIAL end (due to high blood pressures) and net reabsorption near the VENOUS end (low blood pressure, easier to drive reabsorption)

What is the formal definition of RENAL clearance?

Substance is removed from the blood and EXCRETED IN THE URINE "The clearance of a solute is the virtual VOLUME OF BLOOD that would be totally CLEARED OF A SOLUTE in a given TIME"

TRUE or FALSE: A single collecting duct can drain multiple nephrons

TRUE!

TRUE or FALSE: Normal urine composition should have no bacteria present

TRUE!

TRUE or FALSE: As soon as the filtrate leaves the collecting duct and flows into the renal pelvices, it is NOT further modified in composition or volume

TRUE! Once the tubular fluid leaves the collecting duct and flows into the renal pelvises, it is not further modified in composition or volume and it is ultimately excreted out of the body as urine.

TEST: In order to determine if a solute that was filtered was also reabsorbed or secreted, you need to compare what?

The quantity FILTERED and the quantity EXCRETED

TEST: If the clearance of a solute is LESS than the clearance of creatinine, this indicates tubular (reabsorption/secretion)

Tubular REABSORPTION! This makes sense because you know creatinine is excreted as much as it is filtered (no reabsorption or secretion), so if a solutes clearance is less than that then you know it was reabsorbed!

What are some of the normal solutes in urine?

Urea, uric acid, creatinine, Na, K, phosphate, sulfate, Ca, Mg, HCO3-

Without knowing how much solute was reabsorbed or secreted, how do you calculate the quantity of a given solute that is EXCRETED?

Urine flow (V) x urine concentration of the solute (U)!

The vast majority of the volume filtered across all the glomeruli is (excreted/reabsorbed) such that on average, about ___% of the volume filtered is ultimately excreted as urine.

Vast majority of volume filtered is REABSORBED such that about 1% is excreted as urine

What is the equation to calculate fractional excretion (FE)?

[(Ux X Pcr) / (Ucr X Px)] x 100 = FE Ux = conc of solute in urine Px = conc of solute in plasma Pcr = conc of creatinine in plasma Ucr = conc of creatinine in urine

Reabsorption transports solutes through which structures in the kidney?

solutes are transported *from the lumen of the nephron* across epithelial cells THEN into peritubular space/interstitial fluid THEN into peritubular capillaries, *re-entering the circulatory system*

What is glomerular filtration? Through which renal structures does the filtrate flow?

bulk flow of plasma-like fluid from a capillary bed into extra-vascular space in kidneys, filtrate goes from glomerular capillaries -> Bowman's capsule -> proximal tubule of nephron (all due to pressure gradient!)

TEST: What is the role of the distal tubule (and collecting duct)?

hormonally controlled fine tuning of salt and water excretion in small volume of filtrate remaining

What is the major physiologic role of the renal medulla?

maintaining OSMOTIC gradients (movement of water)

On average, how much of the plasma volume entering the afferent arteriole is actually filtered through the glomerulus?

~20%

What is the clearance of PAH, and why?

~600 mL/min, because in addition to being filtered there is a high rate of SECRETION of PAH into the filtrate leaving almost none in the blood. note: from notes beneath slide 32


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