KIDNEY FUNCTION

1. Maintain H2O balance in body 2. Maintain proper osmolarity of body fluid, through regulating H2O balance 3. Regulate quantity and concentration of most ECF ions 4. Maintain proper plasma volume (long term regulation of blood pressure) 5. Help maintain proper acid-base balance (by adjusting H+ and HCO3- balance) 6. Excrete end products of body metabolism i.e. urea, uric acid, bilirubin etc. 7. Excrete many foreign compounds i.e. drugs, food additives, pesticides etc. 8. Produce erythropoietin 9. Produce renin 10. Convert vitamin D into its active form (calcitriol)

NEPHRON
Functional unit of kidney 2 types: cortical and juxtamedullary nephron Cortical nephron: Glomerulus in outer cortex Short loop of Henle slightly dip into medulla Peritubular capillaries form entwine around loop of Henle Peritubular capillaries wrap around proximal and distal tubule Juxtamedullary nephron: 20-30% Glomerulus in inner cortex Long loop of Henle dip deeply into medulla Peritubular capillaries form hairpin vascular loop (vasa recta), which run in close association with loop of Henle Peritubular capillaries wrap around proximal and distal tubule Vascular component: Afferent arteriole carry blood to glomerulus

Glomerulus a tuft of capillaries that filter a protein-free plasma into tubular component Efferent arteriole carries blood from glomerulus and is the only arteriole in body that drain from capillaries Peritubular capillaries supply renal tissue; involve in exchanges with the fluid in tubular lumen Tubular component Bowmans capsule collect glomerular filtrate Proximal tubule uncontrolled reabsorption and secretion of selected substances Loop of Henle establish osmotic gradient in renal medulla that is important in kidneys ability to produce urine of vary concentration Distal tubule and collecting duct variable, controlled reabsorption of Na+ and H2O and secretion of K+ and H+; fluid living collecting duct as urine, which enter renal pelvis Juxtamedullary apparatus- found next to renal corpuscle, contain 2 types of cells Macula densa specialized epithelial (simple columnar) cell at the initial portion of distal tubule adjacent to renal corpuscle; monitor concentration of NaCl in filtrate, effect release of renin by juxtaglomerular cells Juxtaglomerular cell modified smooth muscle cells (granular cell) in afferent arteriole; monitor blood pressure; secrete renin

THREE BASIC RENAL PROCESSES

1. Glomerular filtration nondiscriminant filtration of a protein-free plasma from glomerulus to Bowmans capsule 2. Tubular reabsorption selective movement of filtered substances from tubular lumen into peritubular capillaries

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3. Tubular secretion selective movement of nonfiltered substances from peritubular capillaries into tubular lumen

FORCES INVOLVED FILTRATION

IN

GLOMERULAR

GLOMERULAR FILTRATION
GLOMERULAR MEMBRANE
3 layers: glomerular capillary wall, basement membrane, inner layer of Bowmans capsule Glomerular capillary wall Single layer of flattened endothelial cell Perforated by many large pore (100 times more permeable to H2O and solutes than capillaries elsewhere in body) Not only have traditional pores between endothelial cell, but the cells themselves perforated by large holes/ fenestrations Endothelial cell negatively charged, hinder passage of plasma protein (negative also) Basement membrane Acellular (lack cell) gelatinous layer composed of collagen and glycoprotein that is sandwiched between glomerulus and Bowmans capsule Collagen-provide structural strength Glycoprotein- discourage filtration of small plasma protein; negatively charged, repel plasma protein(also negatively charged) The pore is larger than plasma protein but due to the negative charge, they cant pass through Inner layer of Bowmans capsule Have podocyte- octopus-like cells that encircle glomerular tuft Podocyte have many elongated foot processes that interdigitate with foot processes of adjacent podocyte Filtration slit- narrow slit between adjacent foot processes The epithelial cell of the slit also negatively charged

1. Glomerular hydrostatic pressure (55 mm Hg) Due to diameter of efferent smaller than afferent arteriole Favor filtration 2. Plasma-colloid osmotic pressure (30 mm Hg) Due to unequal distribution of plasma protein across glomerular membrane Oppose filtration 3. Bowmans capsule hydrostatic pressure (15 mm Hg) Oppose filtration Net filtration pressure = 55 30 15 =10 mm Hg = favor filtration

AUTOREGULATION OF FILTRATION RATE (GFR)

GLOMERULAR

By altering afferent arteriolar caliber, adjust resistance to flow through these vessels 80 mm Hg < Autoregulatory range <180 mm Hg 2 intrarenal mechanism: myogenic mechanism (respond to change in pressure within nephrons vascular component; tubuloglomerular feedback (sense change in salt level in fluid flowing through nephrons tubular compartment) Myogenic mechanism i.e. afferent arteriole automatically constrict on its own when it is stretched because of an increased arterial pressure. This limit blood flow into glomerulus to normal despite elevated arterial pressure Tubuloglomerular feedback i.e. if GFR increased due to increased arterial pressure, more fluid than normal filtered and flow through distal tubule. In response to resultant rise in salt delivery to distal tubule, macula densa release ATP and adenosine, both act locally as paracrine on afferent arteriole, cause

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it to constrict, reducing glomerular blood flow and returning GFR to normal.

TUBULAR REABSORPTION
Na+-K+ ATPase MEMBRANE

PUMP

IN

BASOLATERAL

Na+ reabsorbed throughout most of tubule Proximal tubule 67% Loop of Henle 25% Distal and collecting duct 8% No Na+ absorption in descending limb of loop of Henle Na+ from tubular cell is actively pumped into lateral space (interstitial space) by Na+-K+ ATPase pump, keep intracellular [Na+] low, at same time build up [Na+] in lateral space, establish a concentration gradient that favor passive movement of Na+ from its higher concentration in tubular lumen across luminal border of tubular cell. Passive movement of Na+ is always associated with the exchange, co-transport of others solutes, except in collecting duct, it diffuse through Na+ leak channel Na+ continue diffuse down a concentration gradient from its high concentration area in lateral space into surrounding interstitial fluid and finally into peritubular capillary blood

Once secreted into blood, renin act as enzyme to activate angiotensinogen (plasma protein synthesize by liver ) into angiotensin I and on passing through lung via pulmonary circulation angiotensin I converted into angiotensin II by angiotensin-converting enzyme (ACE), which is abundant in pulmonary capillaries. Angiotensin II cause secretion of aldosterone from adrenal cortex

FUNCTION OF RAAS
2 type of tubular cell in distal and collecting tubule : principal (more abundant) and intercalated cells Principal cell- site of action of aldosterone and vasopressin; involve in Na+ reabsorption and K+ secretion (aldosterone); H2O reabsorption (vasopressin) Intercalated cell- acid-base balance Aldosterone increase Na+ reabsorption by promoting insertion of additional Na+ leak channel into luminal membrane and additional of Na+-K+ pump in basolateral membrane Increase Na+ reabsorption increase passive reabsorption of Cl-, RAAS thus promos salt retention and a resulting retention of H2O and rise in BP Angiotensin II- potent constrictor of systemic arteriole, increase BP by increasing peripheral resistance; stimulate thirst, vasopressin (increase H2O retention)

ACTIVATION OF RENIN-ANGIOTENSINALDOSTERONE (RAAS) SYSTEM

Granular cell function as intrarenal baroreceptor , sensitive to pressure change within afferent arteriole. When it detects a fall in blood pressure (BP), it secretes more renin. Macula densa sensitive to NaCl moving past them; trigger increased renin secretion when they detect a fall in NaCl Granular cell innervated by sympathetic nervous system. When BP fall below normal, baroreceptors reflex increase sympathetic activity.

GLUCOSE AND AMINO ACID REABSORBED BY Na+ DEPENDENT SECONDARY ACTIVE TRANSPORT
Sodium and glucose through SGLT (only in proximal tubule) Does not require energy directly, instead use electrochemical gradient establish by primary active transport as driving energy

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Cl- REABSOPTION
Negatively charged Cl- passively absorbed down electrical gradient created by active reabsorption of Na+. For most part, Cl- pass through leaky tight junction between tubular cell into lateral space.

K+ SECRETION DEPEND ON ALDOSTERONE

K+actively reabsorbed in proximal tubule, actively secreted by principal cell

MECHANISM OF K+ SECRETION
Na+-K+ pump transport K+ from lateral space into tubular cell Cause high intracellular [K+], favor net movement of K+ from cell into tubular lumen (passively through leak channel in distal and collecting tubule) By keeping interstitial fluid [K+] low, cause passive movement of K+ out of peritubular plasma into interstitial fluid In principal cell, K+ leak channel concentrated in luminal surface of cell (reason for why K+ secretion in distal and collecting tubule) In proximal tubule, K+ leak channel mostly in basolateral membrane Factor alter secretion of K+: 1. Aldosterone stimulate K+ secretion; rise in plasma [K+] stimulate adrenal cortex 2. Plasma [K+] Proximal tubule Reabsorption Secretion - 67% Na+ actively - variable H+ secretion reabsorbed, Cl- follow depend on acid-base passively body status - All glucose and - organic ion secretion amino acid - PO43- and other electrolytes - 65% H2O passively - 50% urea passively - all K+ Distal and collecting tubule Reabsorption Secretion - Na+, ctrl by - H+, depend on acidaldosterone, Cl- follow base status of body passively - K+ , ctrl by - H2O, ctrl by aldosterone vasopressin

WATER REABSORPTION (PROXIMAL TUBULE)

65% reabsorb in proximal tubule H2O passes primarily through aquaporin (AQP) formed by specific plasma membrane protein in tubular cell AQP-1 in proximal tubule always open AQP-2 in principal cell, regulated by vasopressin In proximal tubule, water reabsorbed due to hypertonicity in lateral space established by active transport of Na+; flow either through leaky tight junction or transcellularly Accumulation of fluid in lateral space cause build up of hydrostatic pressure which flushes water out of lateral space and into interstitial fluid and finally into peritubular capillaries Return of water into plasma enhanced by plasma colloid pressure is greater in peritubular capillaries than in elsewhere

UREA REABSORPTION
Reabsorption of water in proximal tubule produce a [urea] gradient that favor passive reabsorption of urea ([urea] become high in tubular fluid) Only 50% urea reabsorbed due to wall of proximal tubule partially permeable to urea

TUBULAR SECRETION
H+ SECRETION
In proximal, distal, and collecting tubule Extend of secretion depend on acidity of body fluid

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PLASMA CLEARANCE
The volume of plasma completely cleared of that substance by the kidney per minutes Express kidneys effectiveness in removing various substances from internal fluid environment GFR = 125 mL/min 20% of plasma entered glomerulus filtered out produce 180 L of glomerular filtrate/day To calculate clearance rate of substance Y:

] [ ]

If X is filtered but not reabsorbed /secreted, its plasma clearance rate = GFR = 125 mL/min i.e. inulin a harmless foreign carbohydrate produced abundantly by Jerusalem artichokes and to a lesser extent by other root vegetables (i.e. onion, garlic) If Y is filtered and secreted but not reabsorbed, its plasma clearance rate always > GFR If Z is filtered and reabsorbed but not secreted, its plasma clearance rate always < GFR

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