Lecture 11 - Renal II: Glomerular Filtration Rate and the Plasma Clearance

Which substances are almost completely reabsorbed by the kidneys?

Water

Sodium

Glucose

Which substance is 50% reabsorbed and 50% excreted by the kidneys?

urea

___L of fluid is filtered daily while only __L is excreted in the urine

180L

1.5L

glomerular filtration

produces cell-and protein-free filtrate

tubular reabsorption

Selectively returns 99% of substances from filtrate return to the blood in the different renal tubules and collecting ducts

Tubular secretion

Selectively moves substances from blood to filtrate in renal tubules and collecting ducts

How is creatinine in the blood made?

From muscle breakdown

What amount of creatinine filtered by the kidneys is reabsorbed?

0% - none of the creatinine is reabsorbed

Clearance

volume of plasma from which all the substance has been completely removed and excreted into the urine

GFR

glomerular filtration rate

GFR equation

(UxV)/P

- U = urine creatinine conc (mg/ml)

- V = urine flow rate (ml/min)

- P = plasma creatinine conc (mg/ml)

Why is creatinine concentration used to measure GFR?

creatinine is freely (all) filtered

Rearranged GFR equation

(GFR)(P) = (V)(U)

Why creatinine concentration higher in the urine?

A lot of it is filtered and therefore will go to the urine

eGFR

estimated glomerular filtration rate defined by the modification of diet in renal disease (MDRD)

Cockcroft and Gault equation

Ccr = ((140-age) x kg) / (72 x SCr)) (x0.85 for women)

- Ccr = creatinine clearance (ml/min)

- Scr = serum creatinine (mg/dL)

MDRD GFR

unit: ml/min per 1.73m2

GFR according to Cockcroft and Gault equation

GFR = ((140-age) x kg x 1.2 (x0.85 for women))/ Pcr

Can the clearance of urea be used to calculate GFR?

No, 50% is reabsorbed

If plasma clearance of a certain substance is less than GFR what can be assumed?

the substance was reabsorbed

If plasma clearance of a certain substance is more than GFR what can be assumed?

the substance was secreted

Why is it that the lower the GFR, the higher the plasma creatinine?

The lower the GFR, the less effectively the kidneys can filter creatinine from the blood. As a result, creatinine levels in the plasma increase.

PAH

para-aminohippuric acid

PAH excretion

PAH is filtered by the glomerulus and secreted by the proximal tubular cell

Input of PAH

renal artery (Ppah x RPF)

RPF

renal plasma flow

RBF

renal blood flow

Output of PAH

Renal vein + ureter (Upah x V)

What is the average clearance of PAH?

585ml/min (much higher than GFR)

Why is the clearance of PAH so high?

it is also secreted

When PAH is infused at low doses...?

90% of the PAH in the arterial blood is removed in a single circulation circuit

RPF equation

(Upah x V)/(Ppah x Epah)

Epah

Extraction ratio for PAH

What is the maximum secretion rate of PAH?

80mg/min

juxtaglomerular apparatus

Specialized cells (JG and macula densa) next to the glomerulus that help to regulate

- systemic blood pressure

- filtrate formation

Arteriole walls are made of what?

JG cells (granular cells)

JG (granular) cells

enlarged smooth muscle cells - mechanoreceptors; secrete renin

Tubule walls are made of what?

macula densa cells

Macula densa cells

chemoreceptors or osmoreceptors - monitor filtrate & adjust GFR accordingly

Intrinsic mechanisms

Mechanisms built into the kidney to regulate renal blood pressure

- myogenic

- tubuloglomerular feedback

Myogenic mechanism

Smooth muscle cells in afferent arterioles 'react' to increased/decreased blood pressure

Myogenic mechanism in response to increased blood pressure

causes muscle stretch, constriction of afferent arterioles which restricts blood flow into glomerulus

renal autoregulation can maintain constant glomerular filtration rate within __ to __ mm Hg systemic blood pressure.

80 to 180 mmHg

In relation to renal autoregulation what happens during hypovolemic shock? (<70mmHg systemic bp)

renal autoregulation and filtrate formation shuts down

What is smooth muscle's response to being stretched?

it contracts

Myogenic mechanism in response to decreased blood pressure

afferent arterioles dilate which increases renal blood flow

Tubuloglomerular feedback mechanism

flow-dependent mechanism directed by macula densa cells

Tubuloglomerular feedback: slow filtration/low osmolarity

vasodilation of afferent arteriole

Tubuloglomerular feedback: fast filtration/high osmolarity

vasoconstriction of afferent arteriole

Adenosine comes from?

the break down of ATP

Adenosine effect on afferent arteriole

constricts the afferent arteriole

Extrinsic mechanisms

mechanisms external to the kidney that regulate renal blood pressure

- Sympathetic NS

- Renin-angiotensin mechanism

Neural control of renal blood pressure

sympathetic ns, during times of extreme stress, overrides renal autoregulation & shunts blood to heart, brain, skeletal muscles at expense of kidneys

Sympathetic nervous system effect on renal blood pressure

If blood pressure is low, NE and E are released causes systemic vasoconstriction and constriction of afferent arterioles which decreases GFR to restore blood pressure

renin-angiotensin-aldosterone system

There are three pathways for renin release by granular cells.

Renin triggers a cascade of events that increases systemic blood pressure.

Sympathetic NS pathway for renin release by granular cells

1. direct stimulation of granular cells by sympathetic NS to release renin

Aldosterone effect

Retains Na which causes water reabsorption to increase blood volume

Macula densa pathway for renin release by granular cells

Stimulation by activated macula densa cells when filtrate NaCl concentration is low activate the granular cells to release renin

stretch pathway for renin release by granular cells

Reduced stretch of granular cells. These cells act as mechanoreceptors. Decrease blood pressure reduces the tension in the granular cells and stimulates the release of renin.