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Ch 19: The Kidneys Functional unit of kidneys: ?? 4 basic processes of urinary system: Filtration Reabsorption Secretion Excretion

Functions of Kidneys Homeostatic regulation of  H2O & solute concentration – ECF volume – osmolarity, ion concentration

 pH (acid-base balance) Further functions

 Excretion of wastes & foreign substances  Hormone and enzyme production etc.

Four Processes of Urinary System 

Filtration, Reabsorption, Secretion, Excretion

 Related by equation: Figs 19-2/3

E=F-R+S 180 L / day filtered, >99% reabsorbed, 1.5 L / day excreted

Peritubular capillaries Efferent arteriole

Distal tubule

S R

Glomerulus F Afferent arteriole

R S Bowman’s capsule

Proximal tubule

R S

R KEY F

= Filtration: blood to lumen

R

= Reabsorption: lumen to blood

S

= Secretion: blood to lumen

E

= Excretion: lumen to external environment

R Loop of Henle To renal vein

Collecting duct

E To bladder and external environment

1) Filtration = Movement of fluid from blood to lumen of nephron (rel. nonspecific process) Once in lumen – consider it outside body Composition of filtrate?

Fig 19-4

Filtration: Passage across 3 Barriers 1.

Capillary endothelium

2.

Basal lamina (= BM)

3.

Bowman’s capsule epithelium (visceral layer)

Some small molecules (Ca2+, low m.w. fatty acids) bind to plasma proteins  ? Fig 19-4

Cause of Filtration Three types of pressures are at work:

Hydrostatic pressure in capillaries (see exchange in tissues)

Osm. Pin caps > Osm. P in Bowman’s

capsule

Hydrostatic fluid P from presence of

fluid in Bowman’s capsule

Fig 19-6

Net (?) driving pressure: ~ 10 mmHg

Filtration Pressure

Net driving pressure = ?

Glomerular Filtration Rate =

GFR

Describes filtration efficiency: Amount of fluid filtered per unit of time Average GFR ? influenced by  Net filtration pressure  Available surface area

Fig 19-5

GFR closely regulated to remain constant over range of BPs (80 - 180 mm Hg) Goal is to control blood flow though afferent and efferent arterioles – via 1. Reflex regulation  NS & Hormones (e.g.: angiotensin II and prostaglandins)

2. Autoregulation  (myogenic & tubuloglomerular feedback)

Autoregulation via Tubuloglomerular Feedback GFR 

Macula densa cells: release paracrines juxtaglomerular cells (smooth muscle fibers from afferent arteriole):

contract GFR 

Fig 19-10

Distal tubule Efferent arteriole Bowman’s capsule Glomerulus 1 GFR increases. Proximal tubule Macula densa

2 Flow through tubule increases.

4

1

5 Afferent arteriole Granular cells

3 Flow past macula densa increases. 3

2

4 Paracrine diffuses from macula densa to afferent arteriole.

5 Afferent arteriole constricts.

Resistance in afferent arteriole increases. Collecting duct

Loop of Henle

Hydrostatic pressure in glomerulus decreases.

GFR decreases.

Tubular Reabsorption Highly selective and variable

Amount of filtrate / day? Urine production / day? % reabsorbed? Fig 19-5

Mostly transepithelial transport (examples: Sodium and glucose)

Reabsorption may be active (Na+, glucose) or passive (urea) Figs 19-11(!!!) and 13

1 Na+ is reabsorbed by active transport. Filtrate is similar to interstitial fluid.

2 Electrochemical gradient drives anion reabsorption.

1 Na+ 2

Anions 3 Water moves by osmosis, following solute reabsorption.

3 H2O

4 K+, Ca2+, urea Tubule lumen

Tubular epithelium

Extracellular fluid

4 Concentrations of other solutes increase as fluid volume in lumen decreases. Permeable solutes are reabsorbed by diffusion.

Saturation of Renal Transport Same 3 characteristics as discussed in mediated transport Transport maximum determined by 

Saturation  Renal Threshold

Fig 19-14

 Specificity  Competition

Example: Glucose (Fig 19-15)

Secretion 2nd route of entry into tubules for selected molecules Mostly transepithelial transport (analogous to reabsorption). Depends mostly on membrane transport systems (usually 2o active transport)

Provides mechanism for rapid removal of substances (most important for H+, K+, foreign organic ions and drugs such as penicillin etc.)

Excretion = Urine Output Excretion of excess ions, H2O, toxins, "foreign molecules“ "nitrogenous waste“ (NH4+ , urea) Depends on F, R, S (formula ?) Direct measurement of F, R, S impossible  infer from blood & urine analysis Kidneys clean or “clear” plasma of certain substances For any substance: Clearance = plasma volume completely cleared of that substance per minute

Clinical Importance of GFR and Clearance

GFR is indicator for overall kidney function Clearance → non-invasive way to measure GFR (inulin and creatinine) Substance is filtered and reabsorbed but not secreted  clearance rate < GFR Substance is filtered and secreted but not reabsorbed  clearance rate > GFR

Micturition Reflex Spinal cord integration: 2 simultaneous efferent signals In infant just simple spinal reflex Later: learned reflex under conscious control from higher brain centers Various subconscious factors affect reflex Fig 19-18

1

Stretch receptors fire.

2

3

Parasympathetic neurons fire. Motor neurons stop firing.

Smooth muscle contracts. Internal sphincter passively pulled open. External sphincter relaxes.

(b) Micturition Stretch receptors

Higher CNS input may facilitate or inhibit reflex.

Sensory neuron

1

Parasympathetic neuron 2 3

+ – Motor neuron

Internal sphincter External sphincter

3

2

Tonic discharge inhibited

Renal Failure & Artificial Kidney Symptoms when < 25% functional nephrons due to: 1. Kidney infections 2. Chemical poisoning (lead, paint-thinner) etc.

Hemodialysis: 3/week 4-8h/session

Alternative:

CAPD Continuous Ambulatory Peritoneal Dialysis

The End