Renal Handling of Organic Substances

Glucose Amino acids Ascorbic acids Uric acid / Urea Creatine / Creatinine

Renal Handling of Inorganic Substances

Sodium : RAAS / other factors Potassium Magnesium Hydrogen Chloride Bicarbonate

NEPHRON

Parts of the Nephron

PROXIMAL TUBULE

RENAL THRESHOLD (Tm / GFR)

Ultrafiltration is used to transport substances from ic to blood utilizing osmotic or hydrostatic pressure

PASSIVE TRANSPORT Diffusion Facilitated diffusion Osmosis Solvent drag

Equilibrium

Permeability of the membrane Electrochemical gradient

RENAL THRESHOLD (Tm / GFR)

Saturation energy carrier

ACTIVE TRANSPORT Primary active Secondary active cotransport countertransport Endocytosis

Energy Carrier

Glucose

filtration rate = 100 mg/min (Pc x GFR) reabsorption rate = 100 mg/min site = early portion of the proximal tubule It is freely filtered, absorbed by secondary active transport cotransport, the energy is received by Na+s movement into the cell along the gradient. The gradient of sodium is low in the cell because of the Na+ K+ pump. secretion rate = 0 mg/min excretion rate = 0 mg / min Tm = 375 mg/min ideal renal threshold = 300 mg/dL (tm / GFR) actual renal threshold = 200 mg /dL (arterial) 180 mg/dL (venous) splay

PHLORHIZIN

SGLT 2

100 % REABSORBED

GLUCOSE

Amino Acids

filtration rate --- small amount reabsorption ---- 100 %

site -- early portion of the proximal tubule

secretion ---- 0 excretion ----- 0

amino acids amino acids

amino acids
SIMPLE OR FACILITATED DIFFUSION

100 % REABSORBED

AMINO ACIDS

Proteins

peptide hormones, small proteins and small amount of albumin filtration rate = 7.2 g/day (GFR x protein in the ultrafiltrate) reabsorption rate = 7.2 g/day

site --- early portion of the proximal tubule

secretion rate = 0 excretion rate = 0

PROTEINS

100 % REABSORBED

PROTEINS

Urea

filtration rate = 870 mmol/day reabsorption rate = 460 mmol/day site -- mainly in the medullary collecting duct secretion rate = 0 excretion rate = 410 mmol/day (53%) 45/ reabsorbed by diffusion at PT Its not reabsorbed at thin des and asc LH but secreted Its is then reabsorbed back at collecting duct through urea transporter a1. Uta1 is enhanced by ADH This is called the urea cycle. Urea undergoes this cycle about 6 times before being excreted.

UREA

UREA

MAIN SITE OF UREA REABSORPTION DIFFUSION ADH

Uric acid

filtration rate = 50 mmol/day reabsorption rate = 49 mmol/day (98%) secretion rate = 4 mmol/day excretion rate = 5 mmol/day Primarily reabsorbed at PT

Creatinine / Creatine

filtration rate = 12 mmol/day reabsorption rate = 1 (0) mmol/day (98 secretion rate = 1 (0) mmol/day excretion rate = 12 mmol/day Excretion = Filtration Tm = 16 mg/min

Ascorbic acid

excretion rate is regulated by glomerular filtration tubular reabsorption proximal tubule tubular secretion distal tubule ( promoted by adrenal steroid and increased filtered load of sodium) Tm - 2 mg/min Primarily absorbed at PT co-transported with sodium.

Primarily secreted at PT are bile salts, catecholamines, urate, oxalate, drugs.

Potassium

Major cation in the cell. Has to be highly regulated. Regulated by secretion ECF K+ concentration (N = 3.5 - 5.5 meq/L) ICF - 98%, ECF - 2% excretion

kidneys - 90 - 95% feces - 5 - 10% Hyperkalemia cardiac arrest during systole Hypokalemia ca during diastole

K+ intake 100 mEq/day

ECF K+ concentration

ICF K+ concentration

4.2 mEq/L X 14 L 59 mEq K+ output Urine = 92 mEq/day Feces = 8 mEq/day

140 mEq/L X 28 L

3920 mEq

NORMAL K+ INTAKE, DISTRIBUTION OF K+ IN THE BODY FLUIDS AND OUTPUT FROM THE BODY Guyton, Medical Physiology, 2006

filtration rate = 756 mEq/day reabsorption rate = 644 mEq/day (87.8%)

site -- proximal tubule (65%) and thick ascendong loop of Henle (35%) Proximal tubule - absorbance by negative chrge Thick asc LH absorbs by co-transporter. Secreted at collecting duct and distal tubule in exchange with sodium by principle cell and reabsorbed in exchange with hydrogen by the intercalated cell which is stimulated by aldosterone Potassium sparing drug will inhibit p cell.

secretion rate = 31 mEq/day excretion rate = 92 mEq/ day

ASCENDING LOOP PROXIAML TUBULE

Na+ K+ K+
K+

LUMEN

PRINCIPAL CELL

INSTERTITIUM

DISTAL TUBULE COLLECTING DUCT K+

INTERCALATED CELL

Na+ K+
NaK+ pump Electrochemical gradient Permeability of the membrane

65% 4%

POTASSIUM 25 -30%

Increased ECF potassium concentration Increased aldosterone Increased tubular flow rate

12%

Calcium

filtration rate = 540 mEq/day (50%) reabsorption rate = 530 mEq/day (98.2%)

site -- proximal tubule

secretion rate = 0 mEq/day excretion rate = 10 mEq/ day

65% 4 - 9% regulated by PTH CALCIUM 25 -30% PTH

12%

 CALCIUM or PHOSPHATE

VITAMIN D3 ACTIVATION

PTH

INTESTINAL CALCIUM ABSORPTION

RENAL CALCIUM REABSORPTION

CALCIUM RELEASE FROM BONES

Phosphate

excretion is controlled primarily by an overflow mechanism Tm - 0.1 mM/min (renal threshold - 0.8 mM/min) --- decreased by PTH

GFR > Tm ------- excretion of excess PO4GFR < Tm ------- complete reabsorption of PO4-

Magnesium

involved in many biochemical processes, activation of enzymes Primarily reabsorbed at thick ascending LH stored in the bones 99 % - ICF, 1% - ECF 50% - bound to proteins

25% <5% MAGNESIUM 65%

10 - 15 %

Hydrogen

secretion of hydrogen is necessary for both HCO3- reabsorption and formation of new HCO3-. involves in the regulation of acid - base balance Its never reabsorbed but only secreted.

Bicarbonate

filtration rate = 4320 mEq/day reabsorption rate = 4318 mEq/day (99.9%)

site -- proximal tubule, loop of Henle and distal tubules

secretion rate = 0 mEq/day excretion rate = 2 mEq/ day

REABSORPTION OF BICABONATE
PROXIMAL TUBULE REABSORPTION
1. Active transport of Na+ creates an intracellular (-) allowing passive diffusion of Na+ 2. H+ is secreted into the lumen by the Na+ - H+ exchanger 3. H+ combines with the filtered HCO3- to form H2CO3 and then CO2 and H2O 4. CO2 diffuses into the cell to combine with H2O to form H2CO3 then H+ + HCO35. HCO3- returns to the circulation by a Na+ - 3 HCO3cotransporter

H+ SECRETION
EXCRETION OF URINARY BUFFERS
H+ secreted combines with nonbicarbonate buffers in the lumen and is excreted.

SECRETION OF H+ AT THE - INTERCALATED CELL AT THE CORTICAL COLLECTING DUCT

1. Intracellular H20 and CO2 in the presence of carbonic anhydrase form H+ and HCO32. H+ is secreted into the lumen by an active H+ - ATPase pump. 3. HCO3- returns to the circulation via a Cl- - HCO3- exchanger.

85% 4.9% BICARBONATE 10%

1%

FATES OF SECRETED H+
1. 90% TITRATES FILTERED BICARBONATE IN A RECLAMATION PROCESS (H2CO3 ----- CO2 + H2O)
2. 1% IS BUFFERED BY NH3 TO FORM NH4+ 3. 1 % IS BUFFERED BY OTHER TUBULAR BUFFERS MOSTLY HPO4= TO FORM TITRATABLE ACIDITY

4. A VERY MINUTE AMOUNT OF H+ REMAINS FREE IN THE FINAL URINE

Sodium

filtration rate = 25,560 mEq/day reabsorption rate = 25,410 mEq/day (99.4%)

site -- proximal tubule, loop of Henle, distal tubules and collecting duct.

secretion rate = 0 mEq/day excretion rate = 150 mEq/ day

EARLY SEMENT OF PROXIMAL TUBULES

Overview of Sodium Chloride and Water Transport: The Loop of Henle

TAL reabsorbs approximately 25% 30% of filtered NaCl, K, Ca++ and HCO3Descending thin limb reabsorbs approx. 15% of filtered water

Volume regulation and Osmoregulation

Osmoregulation is achieved by changes in water balance, volume regulation primarily by changes in sodium balance.

Volume regulation and Osmoregulation

In summary, regulation of plasma osmolality or osmoregulation is governed by osmoreceptors influencing the release of ADH and thirst. Changes in effective circulating volume is sensed by multiple volume receptors which activate effectors such as aldosterone. ADH increases water reabsorption and therefore increases urine osmolality but does not affect Na+ transport. Aldosterone enhances Na+ reabsorption but not directly that of water.

LATE SEGMENT

65%

5% 9% SODIUM 25% aldosterone

1%

The proximal tubule

The proximal tubule reabsorbs approximately 67% of the filtered water, Na, Cl, K and other solutes. 100% of the filtered glucose, amino acids Also secretes organic cations and anions.