Chapter 14

The Kidneys and Regulation of and Inorganic Ions Functions of the kidneys

Urea, uric , creatinine

Drugs, pesticides, food additives

Amino → glucose in a women Gross anatomy of the Kidney: (1) 11 cm long, 6 cm wide, 4 cm deep, 115-170 g

(2) Right kidney is lower than left kidney

(3) Outer: Cortex → blood filtration 腎錐 Middle: Medulla (8-18 renal pyramids) → collection Inner: papilla → minor calyx → major calyx → → 腎乳頭ureter → 腎盞 腎盂 輸尿管 膀胱

Nephron: 腎元 (1) 1,000,000 /kidney (2) The functionl unit of the kidney (the + the renal ) 腎小球/腎絲球/絲球體 腎小管

To urinary bladder Section of a human kidney

Renal pyramid

Minor calyx Major calyx

Loops of Henle + Collecting ducts

Papilla Basic structure of a 106 nephrons/kidney

腎小體

腎小球

遠曲小管接觸入球微動脈後 鮑氏囊 產生一特化組織 緻密斑

Part of thick segment of ascending limb 亨爾氏套

直管 近髓質腎元 皮質腎元 10-15% 80-85% Nephron types and the Receive 90% of renal blood supply

Renal corpuscle; Glomerular capillaries Glomerular capsule Glomerular (Bowman) capsule

PCT → PST → DTL → ATL → TAL → DCT → CNT → CCD → OMCD → IMCD CD Basic structure of a nephron

Nephron Anatomy of the

近腎小球複合體 JGA

Thick segment of ascending limb Glomerular filtrate Cell-free, protein-free (20% of the plasma)

足細胞

窗孔 Mesangial cells The glomerulus and its filtration barrier

Pore size  70 nm

GFR (glomerular filtration rate)

= Kf [(PGC-PBS) - (GC-BS)] Hydrostatic Colloid osmotic pressure pressure

GC: glomerular capillary BS: Bowmen space

< 5,000 Da

(1) Lamina rara interna (2) Lamina densa Lamina rara externa (3) 濾過裂隙隔膜 TEM of a glomerular capillary and the glomerular membranes

Podocytes (fltration slits)   Endothelia (fenestrae) The juxtaglomerular apparatus (JGA) 近腎小球複合體

系膜細胞 近腎小球細胞

(JG)

Renin JGA The juxtaglomerular apparatus

Tubuloglomerular feedback (TGF)

Adenosine receptor A2 → Dilation

Cl- Na+/K+/Cl- Na+-K+-2Cl- cotransporter

RBF Adenosine (renal blood flow) GFR Gap junctions between juxtaglomerular apparatus (JGA) cells (glomerular filtration → mesangial cells → afferent arteriole rate) Adenosine receptor A1 → Constriction

RAAS (renin-angiotensin- system) angiotensinogen  Renin angiotensin I  ACE (angiotensin-converting enzyme) angiotensin II Tubuloglomerular feedback

AA: afferent arteriole EA:

PUF: capillary hydrostatic ultrafiltration pressure GFR: glomerular filtration rate The three basic components of renal function

@ renal corpuscle

@ varies sites along the tubule

Not all these processes apply to all substances

Amount Amount Amount Amount =+ - excreted filtered secreted reabsorbed Renal handling of three hypothetical filtered substrances Forces involved in glomerular filtration Forces favoring glomerular ultrafiltration

PBS: Bowman space PGC: glomerular capillary hydrostatic pressure  : glomerular capillary colloid osmotic pressure GC + 20 mm Hg + 8 mm Hg Forces controlling fluid reabsorption by

PC  25 mm Hg in all other regions of PC  the body 35 mm Hg

20 mm Hg Other systemic capillary beds  35 mm Hg Control of GFR by constriction or dilation of (AA) or efferent arterioles (EA)

GFR (glomerular filtration rate)

AA: afferent arteriole EA: efferent arteriole Average values for several components that undergo filtration and reabsorption Diagrammatic representation of tubular epithelium

Transcellular route (by transporters)

Paracellular route (by diffusion)

Apical Pathways for reabsorption from the tubule lumen

Determined by structure

Requires the assistance of channels or transporters

ATP-dependent pumps The relationship between plasma glucose concentration and the rate of glucose filtered (filtered load), reabsorbed, or excreted

The maximum rate at which glucose can be absorbed Example of renal handling of inulin The clearance of inulin is equal to the glomerular filtration rate

2-6 cm/s

Transitional epithelium is a type of tissue consisting of multiple layers of epithelial cells which can contract and expand

Circular and longitudinal smooth muscle layers The urinary bladder 腹下神經 SNS: T11-L2, hypogastric nerve (1) detrusor  relaxation (2) bladder neck &  contraction 骨盆神經 PSNS: S2-S4, pelvic nerve (1) detrusor  contraction (2) urethra internal sphincter  relaxation

Transitional epithelium

皺襞

會陰神經 Pudendal nerve from the sacral spinal cord Intravascular ureteral valve preventing urine reflex Control of the bladder Average daily water gain and loss in adults Daily chloride intake and loss Mechanism of Na+ reabsorption in the and cortical collecting duct Coupling of water and Na+ reabsorption The regulation and function of (AQPs) in the medullary-collecting-duct cells to increase water reabsorption

ADH receptor

ADH

Vasopressin-sensitive -insensitive

尿崩症 caused by the failure to release vasopressin or non-respond to vasopressin  25 L/day Generating a hyperosmolar medullary renal interstitium

Countercurrent multiplier system

Impermeable to H2O Simplified depiction of the generation of an interstitial fluid osmolarity gradient by the renal countercurrent multiplier system and its role in the formation of hyperosmotic urine in the presence of vasopressin Functions of the to maintain the hypertonic interstitial recycling Direct and neurally mediated reflex pathways when plasma volume decreases Summary of the renin-angiotensin system and the stimulation of aldosterone secretion by angiotensin II

RAAS (renin-angiotensin-aldosterone system)

ACE

@ cortical collecting ducts Pathways by which decreased plasma volume leads to increased Na+ reabsorption Atrial natriuretic peptide (ANP) increases Na+ excretion

Cortical Osmoreceptor pathway that decreases vasopressin secretion and increases water excretion when excess water is ingested

ADH

Medullary Baroreceptor pathway by which vasopressin secretion increases when plasma volume decreases

Medullary Pathways by which Na+ and water excretion decrease in response to severe sweating Inputs controlling thirst Simplified model of the basic renal processing of Pathways by which an increased potassium intake induces greater K+ excretion Summary of the control of aldosterone and its effects on Na+ absorption and K+ secretion Summary of “Division of labor” in the renal Sources of hydrogen ion gain and loss - Reabsorption of HCO3

H+-ATPase or Na+/H+ countertransporters H+/K+-ATPase pumps - Renal contribution of new HCO3 to the plasma as achieved by tubular secretion of H+

H+-ATPase or Na+/H+ countertransporters H+/K+-ATPase pumps - Renal contribution of new HCO3 to the plasma as achieved by + renal metabolism of glutamine and excretion of ammonium (NH4 )

Proximal tubule Renal responses to and + - Changes in the arterial concentrations of H , HCO3 , and carbon dioxide in acid-base disorders Simplified diagram of hemodialysis

400 mL/min

1000 mL/min