L-43 Overview Of Renal Function

Front 1

Functions of kidney

Back 1

1. Maintain homeostasis despite waste products of diet and metabolism, and environmental and clinical changes

2. Secrete hormones - renin, angiotensin II, prostaglandings, bradykinins, erythropoietin, 1,2(OH)2 vitamin D3 (calicitriol)

3. Catabolize peptide hormones - e.g. insulin which persists in kidney disease

4. Organ of gluconeogenesis, secondary to liver

Front 2

Amount of filtration per day

Back 2

150-180 L/day

Front 3

Glomerulus

Back 3

Has capillary tangle from which absorption occurs into Bowman's space

Has endothelial cells and specialized epithelial cells (podocytes) with interdifitating foot processes that wrap capillary network and line Bowman's capsule - visceral and parietal epithelial

Front 4

Distal tubule

Back 4

In apposition to arterioles

Senses transit of solutes, communicates to arterioles through macula densa

Whole apparatus is juxtaglomerular apparatus

Front 5

Filtratoin barrier

Back 5

Composed of:

Fenestrated endothelium lining capillary lumen

Basement membrane of glomerulus - made of type 4 collagen and negatively charged moieties i.e. heparan sulfate.

Bowman's capsule with epithelial foot processes separated by spaces

Front 6

Particles filtered by filtration barrier

Back 6

RBCs and large proteins remain in blood

Medium sized proteins are slowed

Plasma water and solutes pass freely

Front 7

Layers of kidney

Back 7

Cortex - glomeurulus and promximal tubules

Outer medulla - superficial glomerulus' Loops of Henle

Inner medulla - Juxytomedullary glomerulus' Loops of Henle

Collecting duct has cortical, outer medullary, and inner medullary portions

Front 8

Nephron

Back 8

Glomerulus to distal tubule

(Collecting ducts are shared and embryologically distinct from rest of nephron)

Front 9

Blood supply to nephron

Back 9

Afferent aa. -> glomerulus -> efferent aa.

Efferent arterioles gives rise to peritubular capillary network which removes reabsorbed molecules and secretes secreted molecules.

Juxtamedullary nephrons also have thin straight capillaries, vasa recta, which travel with Loop of Henle and help create high osmolality in medullary interstitium.

All blood empties to renal vein.

Front 10

Standard processes of nephron

Back 10

Filtration - across glomerulal capillary basement membrane. Only fraction of plasma water is filtered.

Secretion - from peritubular capillaries to tubule

Reabsorption - from tubule to peritubular capillaries

Scenarios include: filtration with complete secretion, filtration with complete reabsorption, and filtration with net reabsorption (less appears in urine than initially filtered)

Front 11

Reabsorption of key ions

Back 11

Water - 98-99% absorbed

Na+ - 99% reabsorbed. Some excreted because modern diet is Na+-rich.

HCO3- - 100% reabsorbed

K+ - 85-95% reabsorbed. Abundant in diet so partly excreted.

Urea - 40-50% reabsorbed. Keep some to help conserve water.

Front 12

Clearance

Back 12

Removing substance from circulation either by transformation (metabolism) or removal by kidney (renal clearance)

Clearance can be described by:

- Rate - amount of solute removed/unit time

- Half life

- Volume of plasma/unit time from which all of substance is removed (mL/min or L/day)

Front 13

Inulin

Back 13

Freely filtered and neither secreted nor reabsorbed. Filtered inulin = secreted inulin

GFR * Pin = V * Uin, where V = urine flow rate, Pin = plasma inulin concentration

GFR = V * Uin/Pin = 125 mL/min

Front 14

Creatinine

Back 14

Creatinine behaves like insulin - filtered almost completely at glomerulus but a little secretion.

Continuously produces as creatine by muscle and proportion to muscle mass. Stable for each person.

Metabolized to creatinine in liver

Endogenous so does not have to be administered.

Front 15

Creatinine clearance

Back 15

C(creatinine) = V * Ucr/Pcr

We can measure flow rate as mL/day instead of mL/minute and then divide by 1440 min/day.

Front 16

Relationship between plasma creatinine and GFR

Back 16

Inverse relationship between plasma creatinine and GFR.

GFR = V*Ucr/Pcr

Pcr = V*Ucr/GFR

Kidney disease leads to loss of glomerular filtration surface area, reducing GFR and raising plasma creatinine.

Front 17

Result of removal of kidney on GFR, creatinine production and excretion of plasma creatinine

Back 17

GFR immediately drops to 50%.

Creatinine production remains same (function of muscle mass). Creatinine excretion rapidly drops but then increases until baseline because...

Plasma creatinine increases to double so that a normal amount remains excreted.

Front 18

Compensatory hypertrophy

Back 18

After removal of kidney, growth of contralateral kidney (tubular cell hypertrophy and hyperplasia without new nephrons because glomerulogenesis complete by 32 weeks gestation)

Overall GFR is normalized due to increase in single nephron GFR

Front 19

Cases where compensatory hypertrophy is incomplete

Back 19

Chronic renal disease of other kidney - single nephron GFR already augmented

Elderly - progressive loss of glomeruli, impaired ability to augment SNGFR

Growth restricted infants (maternal starvation, placental insufficiency)

Front 20

Urea clearance

Back 20

Curea = V * Uurea/Purea = 70mL/min

Urea is freely filtered and partially reabsorbed so clearance < GFR.

Urea clearance varies with water balance and need to use urea to conserve H2O.

Front 21

RPF

Back 21

Paraaminohippurate (PAH) is both filtered at glomerulus and secreted at tubules.

All of PAH will appear in urine and none in renal vein.

P(pah in artery) * RPF (artery) = (P(pah in vein) * RPF(vein)) + (Upah * V)

Vein term cancels out because PAH is not found in veins.

RPF = V * Upah/P(pah in artery) = 625 mL/min

Front 22

Renal blood flow

Back 22

Renal blood flow = RPF/1-hematocrit = 1300 mL/min, or 20% of cardiac output

Front 23

Filtration fraction

Back 23

GFR/RPF = 125/625 = 0.2

20% of plasma water is filtered at glomerulus

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