Overview of Kidney Function

Transcription

1 The Kidney

2 Overview of Kidney Function osmolarity of the body fluids volume of ECF plasma ph waste products (urea, uric acid, creatinine, foreign compounds) synthesis of: - EPO, renin, kallikrein, prostaglandins, thromboxane - active form of D3 - gluconeogenesis

3 Cortex Medulla Renal hilium Renal artery Renal vein Renal pelvis Ureter Kidney Anatomy Medullary pyramids Renal sinus (with fatty tissue) Renal capsule Major calyx Minor calyces Kidney localization: posterior to the parietal peritoneum Urine flow: pyramid papilla minor calyx major calyx renal pelvis ureter bladder

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5 Nephron Renal corpuscle: Bowman s capsule (2 layers; internal parietal composed of podocytes, visceral external composed of simple squamous epithelium), and glomerulus Renal tubules: PCT, loop of Henle, DCT

6 Podocytes The visceral layer of the renal corpuscle is a very specialized epithelium: it takes the form of podocytes Slide 6

7 Connecting tubule Distal convoluted tubule Cortex Outer medulla Inner medulla Cortical collecting duct Thick ascending limb Inner medullary collecting duct Proximal convoluted tubule Renal corpuscle Containing Bowman s capsule and glomerulus Proximal straight tublue Outer medullary collecting duct Thin descending limb Thin ascending limb Tubules: Bowman s capsule Proximal tubule Loop of Henle Distal Collecting duct

8 Cortex Outer medulla Superficial cortical glomerulus Peritubular capillaries Afferent arteriole Efferent arteriole Cortical radial artery Cortical radial vein Juxtamedullary glomerulus Arcuate artery Arcuate vein Descending vasa recta Artery Aff. arteriole Glomerulus (high P) Eff. arteriole Peritubular cap.(low) Vein Inner medulla To renal vein From renal artery Ascending vasa recta Blood supply to kidney is derived from efferent arterioles

9 Afferent arteriole Renal nerves Granular cells Juxta. appar. = Thick ascending limb Macule densa Efferent arteriole Extraglomerular mesangial cells Urinary space Bowman s capsule Proximal tubule Glomerular capillaries aff. and eff. arterioles + ascending limb + extraglomerular mesangial cells

10 Blood through the kidney/min 1200ml/min blood flow 125ml/min glomerular filtrate 124ml/min glomerular filtrate is reabsorbed How much urine? ~ 1ml/min

11 Kidney innervation Sympathetic: X, XI, XII and lumbar spinal nerve Sympathetic effect: vasoconstriction and renin release; increased sodium reabsorption

12 Sympathetic NS Volume depletion SNS AVP H 2 O reabsorption from collecting duct SNS Na +, Cl -, H 2 O reabsorbed by proximal tubules

13 Urine Formation Glomerular filtration: high capillary pressure allows passage of compounds less than 10K MW Filtration Kidney tubule Glomerulus Reabsorption Secretion Excretion Peritubular capillary

14 Tubular reabsorption: selective transfer of compounds from tubule fluid back to plasma Filtration Kidney tubule Glomerulus Reabsorption Secretion Excretion Peritubular capillary

15 Tubular secretion: selective transfer of compounds (e.g., H + ) from plasma to tubule fluid Filtration Kidney tubule Glomerulus Reabsorption Secretion Excretion Peritubular capillary

16 Kidney exretory processes

17 Kidney exretory processes Filtration in Bowman's Capsule Reabsorption in the Proximal Tubule Creation of an Osmotic Gradient in the Loop of Henle Regulating Water and Electrolyte Balance in the Distal Tubule and the Collecting Duct

18 Filtration in Bowman's Capsule

19 Glomerular filtrate Plasma capillary endothelium podocyte basement membrane (large molecules do not pass) glomerular filtrate

20 Filtration (10% of blood volume) requires high blood flow rate 1200ml/min; cortex rate > medulla rate. Autoregulation (80-180mmHg): raised MAP aff. arteriole constriction maintain constant filtration rate Sympathetic drive (low MAP) vasoconstriction

21 Substances influencing renal blood flow Vasoconstrictors: Angiotensin II Endothelin Epinephrine Norepinephrine Thromboxane Vasodilators: Bacterial pyrogens Kinins Nitric oxide Prostaglandins (PGE2, PGI2)

22 Filtered compound must pass capillary fenestra, basement membrane, and slit pore Almost all of filtered K + is reabsorbed in proximal parts of nephron Most of excreted K + is secreted by collecting ducts Glucose is copmpletely reabsorbed Creatinine is excreated without reabsorption Urea and uric acid reabsorbed to some extend

23 Filtration press. = filtr. coeff.x (glom. hydrostat. capsule hydrostat. - plasma oncotic) Capsule hydrostat provides tubule flow; plasma oncotic is from lack of protein filtration. Afferent arteriole Glomerulus Urinary space Efferent arteriole

24 GFR changes Constriction of aff. aretrioles downstream glom. pressure blood flow GFR Dilation of aff. aretrioles glom. hydrost. press. and blood flow GFR Dilation of eff. aretrioles glom press blood flow GFR Constriction of eff. aretrioles upstream glom. pressure blood flow Modest constriction - GFR ( in glom. press. predominates than blood flow) Severe constriction - GFR ( blood flow predominates)

25 GFR changes Obstruction of urinary tract hydrost. press. in Bowman s capsule GFR in plasma protein concentr. GFR

26 Determination of GFR is one of the most important measurements of kidney function

27 Clearance of compound x = (urine conc.)(urine flow rate)/plasma conc. C x = U x V/P x Filtered inulin Excreted inulin Since inulin is filtered and not reabsorbed, inulin clearance equals GFR.

28 Endogenous creatinine clearance approximately equals GFR, and is thus used clinically If GFR decreases creatinine and urea accumulate in blood

29 Proximal tubule endocytosis reabsorbs protein; glomerular leakiness causes proteinuria. PAH (p-aminohippuric acid) is very actively secreted by PCT; all the blood that passes through the kidney is cleared of PAH. Therefore, the PAH clearance rate is equal to the kidney blood flow rate; clinically used.

30 Glomerulus

31 Reabsorption in proximal tubule

32 LUMEN OF TUBULE (luminal membrane) Tight junction Luminal cell membrane Microvilli (brush border) Endocytic vesicle BLOOD SIDE (basolateral membrane) Lateral intercellular space Basal infolding and process from adjacent cell Basement membrane Nucleus Mitochondria Poximal convoluted tubule (PCT) cells have luminal (microvilli) and basolateral (ridges, mitochondria) membranes. Basolateral cell membrane (c) 2003 Brooks/Cole - Thomson Learning

33 Na+/K+ ATPase PCT The gradient created by the Na+/K+ ATPase provides a potential to allow Na+ contransporters reabsorb nutrients and electrolytes. Water also flows in via osmosis Solutes exit the epithelial cells and enter the blood Water flows from the epithelial cells into the blood via osmosis

34 PCT - function Na + absorption H 2 O absorption Glucose absorption Amino acids absorption Vitamin C absorption

35 Sodium reabsorption is the major activity of the kidney tubules; 80% of oxygen consumed by the kidneys is devoted to powering active Na + reabsorption How does sodium reabsorption affect the reabsorption of water and other substances?

36 Handling of Important Electrolytes Glucose amino acids phosphate Tubule lumen Interstitial space Lateral intercellular space Proximal tubule cell Peritubular capillary Na + reabsorption controls blood Na +, H 2 O and solute reabsorption, and H +, K + secretion. Tight junction NaCl 70% of Na + and H 2 O are reabs. in PCT

37 Glucose reabsorption (secondary active transport)

38 Glucose is reabsorbed by proximal tubule cells via Na + /glucose cotransport. Proximal tubule cell ATP Tubule lumen Glucose Glucose Active transport ADP Peritubular capillary blood Glucose Luminal cell membrane Cotransport Facilitated diffusion Glucose Basolateral cell membrane

39 At threshold: Filtered load of glucose tubular transport maximum for glucose (T m G) At threshold Filtered Reabsorbed Excreted

40 Glucosuria Excretion of glucose loss of water and salt increased urination, dehydration and thirst (symptoms of diabetes mellitus)

41 There are several types of Na + /amino acid cotransporters in the proximal tubule. 90% of filtered uric acid (end product of purine metabolism) is reabsorbed in proximal tubule.

42 Distal convoluted tubule Collecting duct Proximal convoluted tubule Cortex Outer medulla Urea (formed in the liver): Proximal tubule reabsorbs Loop of Henle secretes Collecting duct reabsorbs Vasa recta Loop of Henle Inner medulla

43 Urea production dialysis Tissue trauma Internal bleeding Infection Fever

44 Gout Uric acid crystals precipitate in the joints (often in a great toe) Treatment: probenecid high dose ASA sodium bic. + water intake

45 Proximal tubule and loop of Henle reabsorb filtered K + ; collecting duct principal cells secrete excess K +. Tubule lumen Cortical collecting duct principal cell Blood

46 PCT

47 Creation of an Osmotic Gradient in the Loop of Henle

48 The kidneys save water when they produce a hyperosmotic urine Osmolality = osmoles per kilogram of H 2 O Osmolarity = osmoles per liter of solution Biological fluids are mostly water, so the two terms are practically identical Only mammals and birds can produce urine that is osmotically more concentrated than is the blood

49 The descending limb of the loop is highly permeable to water but almost completely impermeable to solutes The lower portion of the ascending branch of the loop of Henle, however, is highly permeable to Na + and Cl -, moderately permeable to urea, and almost completely impermeable to water When the filtrate reaches the hairpin turn, it is isotonic with the surroundig medium (about 1200 mosm/l)

50 As it travels up into the less-concentrated regions of the medulla, Na + and Cl - will passively diffuse across the membrane As the filtrate continues up the thick portion of the loop of Henle, Na + and Cl - are actively pumped out of the filtrate into the surrounding medium. This requires energy, but helps to maintain the osmotic concentration gradient in the medulla.

51 Loop of Henle

52 The water and solutes that flowed into the medulla can be reabsorbed by the vasa recta

53 Loop of Henle is countercurrent multiplier; vasa recta is countercurrent exchanger. Stepwise shift of fluid Development of single effect

54 Regulating Water and Electrolyte Balance in the Distal Tubule and the Collecting Duct

55 plasma Na + aldosterone reabsorption of Na + and Cl - in the distal tubule. Water flows into the tubule via osmosis. Dehydration ADH (antidiuretic hormone) This causes aquaporin channels to be inserted in the membrane of the collecting duct H 2 O reabsorption

56 Ascending loop pumps out NaCl, while descending loop allows H 2 O to flow out. With high ADH, collecting duct H 2 O osmotically flows out to produce concentrated urine. The vase recta vase recta reduces medulla ISF (interstitial fluid) dilution by incoming isoosmotic blood; carries away H 2 O + solutes.

57 Diabetes insipidus ADH deficiency large amounts of dilute urine elevated drinking Low ADH prevents osmotic water loss from the collecting duct hypoosmotic urine.

58 No ADH Present - Collecting Duct is NOT permeable to water and large volume of urine is produced ADH Present - Collecting Duct is permeable to water and a small volume of urine is produced

59 Distal convoluted tubule - function Absorption H 2 O Na + Calcium phosphate Secretion H + K +

60 Ca ++ output is 90% fecal and 10% urinary; parathyroid hormone (PTH) raises Ca ++ reabsorption. PO 4 output is mostly urinary; filtered PO 4 above T m (maximal transport) is excreted; parathyroid (PTH) lowers PO 4 reabsorption.

61 Collecting ducts

62 Neural pathways for urination Most S1-S3

63 Excretion of Urine Calyx pacemaker cells electrical waves peristalsis waves in ureters urine flow Parasympathetic pelvic nerves + sympathetic hypogastric nerves bladder smooth muscle Somatic pudendal nerves external sphincter; all three nerves have sensory and motor Stretch receptors bladder contraction + sphincter relaxation; ureter flow reinforces