Kidney Function: Feedback, Thresholds & Reabsorption

Tubuloglomerular Feedback Mechanism

• Granular (JG) cells monitor the amount of stretch of the afferent arteriole
• Increased stretch prompts vasoconstriction of the afferent arteriole
• Macula densa cells release ATP in response to fast flowing filtrate
• A rise in glomerular blood pressure prompts vasodilation of the efferent arteriole

Renal Thresholds for Glucose

• A plasma concentration of glucose of 340 mg/100 ml means that glucose will appear in the urine
• At this level, the amount appearing in the urine is 50 mg/min
• 340 x 1.25 = 425 mg filtered per minute
• 425 – 375 = 50 mg glucose excreted per minute
• Plasma concentration of substance × GFR = Amount of substance filtered
• For example, 100 mg glucose/100 ml plasma x 125 ml plasma filtered/min = 125 mg glucose filtered/min

Tubular Reabsorption

• Transcellular reabsorption is similar to absorption by intestinal epithelial cells
• Paracellular reabsorption primarily involves H₂O and some ions (Ca++, Mg++, K+ and some Na+) and occurs mainly in the PCT where the tight junctions are more leaky
• 80% of ATP used for Active Transport (AT) reabsorbs sodium and creates gradients supporting everything else, including water
• 2º AT is used for glucose, amino acids, some ions and vitamins

Passive Tubular Reabsorption

• Include diffusion, facilitated diffusion, and osmosis
• Occurs along an electrochemical gradient, not requiring ATP
• Active reabsorption of Na+ pulls anions (especially Cl-)
• Obligatory water reabsorption results from Na+ transport, with aquaporins in the PCT
• As water leaves, gradients are created for reabsorption of other substances, especially if they are lipid-soluble

Substances Partially or Not Reabsorbed

• These substances either have no carriers, are not lipid soluble, or are too large
• They are primarily nitrogenous end products of protein and nucleic acid metabolism
• Urea is a main nitrogen-containing end product, with 50-60% reclaimed, with small size for diffusion through pores
• Creatinine is a large, lipid-insoluble waste from muscles, not reabsorbed by the kidneys
• Uric acid is an end product of purine metabolism, where too much leads to problems

Tubular Reabsorption Regions and Substances

• PCT reabsorbs all glucose and amino acids, 65% of Na+ and K+, 65% of H2O, 90% of bicarbonate, and 50% of Cl
• The Loop of Henle's ascending and descending limbs function differently, with water leaving the descending limb and NaCl and K+ leaving the ascending limb
• In the DCT and collecting duct, hormonally regulated reabsorption is determined by body hydration level, reabsorbing only 10% NaCl & 20% of water
• Antidiuretic hormone (ADH), the Renin-angiotensin system + aldosterone, and Atrial natriuretic peptide (ANP) are key hormones

Four Functions Associated with Tubular Secretion

• Kidneys use secretion to rid the body of unwanted substances: not reabsorbing or secreting them into the urine
• This involves mainly H+, K+, creatinine, NH4+, uric acid, urea
• Secretion happens mostly in the PCT, but also in the late DCT and early collecting ducts
• Functions of secretion:
• Dispose of substances not in the original filtrate, such as certain drugs or metabolites bound to plasma proteins
• Dispose of substances that underwent passive reabsorption, such as urea and uric acid
• Dispose of excess K+ ions
• Maintain blood pH

Countercurrent Mechanism & Medullary Osmotic Gradient

• The purpose is to regulate urine concentration and volume
• Water and salt are reabsorbed in PCT; filtrate at top is 300 mOsm
• Differing permeabilities cause water, then salt to be reabsorbed
• The descending limb is relatively impermeable to solutes and permeable to H2O: Water moves freely out by osmosis
• Filtrate osmolarity can reach 1200 mOsm by the "elbow" of loop of Henle within juxtamedullary nephrons

Loop of Henle

• Ascending limb is impermeable to water; actively transports Na+, Cl, K+ out via Na+-K+-2Cl- cotransporter, preventing water movement
• Positive feedback (countercurrent multiplier) increases filtrate concentration at each level of descending limb, making it ~200 mOsm more concentrated
• The net effect is to reduce filtrate volume

Vasa Recta

• The vasa recta functions as a countercurrent exchanger to maintain the osmotic gradient
• 15% are medullary nephrons
• Blood flow is sluggish, and vessel walls are permeable to salt and water
• Act as an exchanger and doesn't

Formation of Dilute Urine

• Happens when the body is overhydrated
• Filtrate at the top of ascending limb is dilute due to salt removal
• Without ADH, the collecting ducts remain impermeable to water & very dilute urine produced
• Urine osmolarity can be as low as 100 mOsm

Concentrated Urine

• ADH acts at collecting ducts, increasing the number of water channels in principal cells
• Collecting ducts extend into medullary area, the filtrate can again attain an osmolarity up to 1200 mOsm
• Facultative water reabsorption is regulated, and variable based on body's needs
• Constant low level of ADH rises with increased plasma osmolarity above 300 mOsm, needed for urine concentration
• ADH depends on the medullary gradient & urea

Diuretics

• Diuretics cause enhanced urinary output
• A diuretic is any substance that is not reabsorbed, or exceeds renal reabsorption ability
• Caffeine and most prescribed diuretic drugs inhibit Na+ reabsorption

Renal Clearance

• Is the volume of plasma from which a substance is 100% cleared per unit time
• RC = UV/P
• U: [substance(mg/ml)] in urine
• V: flow rate of urine formation (ml/min)
• P: [substance(mg/ml)] in plasma
• Inulin, a high MW polysaccharide, used as a standard since it is not stored, reabsorbed or secreted by kidneys
• RC (inulin) = GFR

Physical Characteristics of Urine

• Colour & transparency: should be clear/pale to deep yellow, from pigment urochrome
• Odour: will develop ammonia odor if left to stand, will relate to the metabolism of the urea
• pH: usually ~ is around 6 pH
• specific gravity: usually 1.001 to 1.035

Chemical Composition of Urine

• 95% water, 5% solutes
• Solute in highest concentration is
• Contains uric acid and creatinine
• In decreasing order: urea, Na+, K+, phosphate, sulfate, creatinine, uric acid constituents
• Variable levels of Ca++, Mg++, HCO3