Functional Anatomy of Kidney and Nephrons

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Functional Anatomy of KidneyStructure and
Function of NephronsRenal Blood Flow and its
Regulation
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Kidneys

• Kidneys are a pair of excretory organs situated
  on the posterior abdominal wall, extending from
  upper border of T12 to L3 vertebra
• Right kidney is slightly lower than the left
• Each kidney is 11 cm long, 6 cm broad and 3 cm
  thick, weight 150 g in males and 135 g in females
• Capsules or coverings of kidneys - Fibrous
  capsule, Peri-renal fat, Renal fascia and
  Para-renal fat
• Coronal segment cortex medulla renal sinus

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• Renal cortex
• Cortical lobules - which form caps over the bases
  of the pyramids
• Renal columns - which dip in between the pyramids
• Renal medulla
• has 10 conical masses called renal pyramids,
  their apices form renal papillae

• Renal sinus
• Space that extends into kidney from hilus
• Contains branches of renal artery and renal vein
• Renal pelvis divides into 2-3 major calices and
  these in turn divide into 7-13 minor calices,
  each minor calyx (cup of flower) ends in an
  expansion which is indented by 1-3 renal papillae

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• Histologically, each kidney is composed 1-3
  million uriniferous tubules. Each consists of
• Secretory part - which forms urine is called
  nephron, functional unit of kidney
• Nephrons open in to collecting tubules. Many such
  tubules unite to form the ducts of Bellini which
  open into minor calices
• Arterial Supply
• One renal artery on each side arising from
  abdominal aorta
• At or near hilus, renal artery divides into
  anterior and posterior branches giving rise to
  segmental arteries
• Lymphatics
• Lateral aortic nodes
• Nerve Supply
• Renal plexus (an off shoot of coeliac plexus,
  T10-L1)

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• Circulation of renal blood flow

Renal artery divides serially into interlobar
artery ? arcuate ? interlobular arteries ?
afferent arterioles ? capillary tufts of renal
glomeruli into outer cortex ? efferent arterioles
? in juxtamedullary zone ? arterioles become vasa
recta (closely applied to loop of henle) Venous
drainage Stelate veins ? interlobular veins ?
arcuate veins ? interlobar veins
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• Two types of nephrons are present
• Cortical nephrons with short loop of Henle
• Juxtamedullary nephrons with long loops of Henle

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• Glomerulus - Five components
• Capillary endothelium 70-100 nm fenestrations
  restricts passage of cells
• Glomerular basement membrane filters plasma
  proteins
• Visceral epithelium podocytes with s foot
  processes with 25-60 nm gaps, permeability
  altered by contraction of foot processes
• Parietal epithelium (Bowmans capsule)
• Mesangium (interstitial cells) pericytes,
  structural support, phagocytosis, restricts bld
  flow in response to angiotensin-II

Filtration barrier
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• Filtration barrier - Size and charge selective
• Charge all 3 layers contain negatively charged
  glycoproteins ? restricts passage of other
  negatively charge proteins
• Size Molecules with radius lt1.8 nm ? water,
  sodium, urea, glucose, inulin ? freely filtered
• gt3.6 nm ? hemoglobin and albumin ? not filtered
• Between 1.8-3.6 ? cations filtered, anions not
• Glomerulonephritis ? negatively charged
  glycoproteins destroyed? polyanionic proteins
  filtered ? proteinuria

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• Glomerular Filtration Rate (GFR)
• Normal GFR in men 125 ml/min, 10 lower in
  females
• Depends on permeability of filtration barrier
• Difference between hydrostatic process pushing
  fluid into Bowmans space and osmotic forces
  keeping fluid in plasma
• GFR Kuf (Pgc Pbs) (?gc ?bs)
• Pgc Pbs Hydrostatic pressure in glomerular
  capillary and basement membrane
• ?gc ?bs plasma oncotic pressure in
  glomerular capillary and basement membrane
• Kuf Ultrafiltration coefficient reflects
  capillary permeability and glomerular surface area

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• Juxtaglomerular apparatus
• Macula densa modified portion of thick
  ascending limb which is applied to glomerulus at
  the vascular pole between the afferent and
  efferent arterioles containing chemoreceptor
  cells which sense tubular concentration of NaCl
• Granular cells Produce renin, which catalyses
  the formation of angiotensin ? modulates efferent
  and afferent arterial tone and GFR

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• Functions
• Nephron regulates
• Intravascular volume, osmolality, acid base
  balance, excrete the end product of metabolism
  and drugs
• Urine is formed by combination of glomerular
  ultrafiltration tubular reabsorption and
  secretion
• Nephron produces hormones
• Fluid homeostasis (renin, prostaglandins, kinins)
• Bone metabolism (1,25-dihydroxycholecalciferol)
• Hematopoiesis (erythropoietin) produced by
  interstitial cells in peritubular capillary bed
  (85 ? stimulus hypoxia

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• Renal autoregulation
• Enables the kidney to maintain solute and water
  regulation independently of fluctuations in
  arterial blood pressure
• Kidney maintains a constant renal blood flow and
  GFR through renal arterial range of 80-180 mmHg

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Afferent and efferent control mechanism
(myogenic) Renal vascular resistance ? Mediated
by variable resistance of afferent arterioles ? ?
mean arterial pressure ? ? renal vascular
resistance(? tone, dilatation of afferent
arterioles) ? Myogenic response ? Renal blood
flow and GFR maintained ? Vice versa, afferent
arterioles constrict in response to ? MAP
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Afferent and efferent control mechanism (myogenic)
GFP 60 mmHg (N), i.e. 60 of MAP
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Tubuloglomerular feedback ? GFR ? ? delivery of
NaCl to distal tubule ? ? Cl- sensed by macular
Densa cells ? Release of renin (from afferent
arterioles) ? Angiotensin ? Arteriolar
constriction ? GFR and RBF
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Distribution of renal bld flow between the cortex
medulla
Cortex Medulla
Percent renal blood flow 94 6
Blood flow (mL/min/g) 5.0 0.03
PO2 (mm Hg) 50 8
O2 extraction ratio (VO2 /DO2 ) 0.18 0.79
DO2 Oxygen delivery, VO2 Oxygen consumption

• The renal medulla receives only a small fraction
  of the total renal blood flow, and flow rates are
  extremely slow
• As a result, tissue oxygen tension is extremely
  low, and the medulla extracts almost 80 of the
  oxygen delivered to it
• A very mild reduction in total and cortical renal
  blood flow may therefore induce ischemia and
  hypoxia in the renal medulla

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Hormonal Regulation

• Normally, a balance is present between systems
  promoting renal vasoconstriction and sodium
  retention versus systems promoting renal
  vasodilation and sodium excretion.
• Surgical stress, ischemia, and sepsis tip the
  balance in favor of vasoconstriction and sodium
  retention.
• On the other hand, hypervolemia (or induction of
  atrial stretch) tips the balance in favor of
  vasodilation and sodium excretion.

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Epinephrine norepinephrine ? ? Afferent
arterial tone (directly preferentially) ? Marked
? in GFR prevented indirectly by release of
renin and angiotensin-II
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• Renin angiotensin and Atrial natriuretic peptide
  (ANP)
• Hypotension or hypovolemia ? renin ? afferent
  arteriole ? angiotensin II ? release of
  aldosterone from the adrenal cortex
• Volume reexpansion causes atrial distention ?
  release of ANP
• ANP inhibits the release of renin, renin's action
  on angiotensinogen to form angiotensin II,
  angiotensin-induced vasoconstriction, stimulation
  of aldosterone secretion by angiotensin II, and
  action of aldosterone on collecting duct

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Prostaglandins Systemic hypotension and renal
ischemia ? Angiotensin induced prostaglandin
synthesis (PGD2, PGE2 PGI2) ? Vasodilation
(protective mechanism)
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Neuronal Regulation

• Sympathetic outflow from spinal cord
• ?
• Celiac renal plexus
• ?
• ?1 receptors ? sodium reabsorption in PCT
• ?
• ?2 receptors ? Na reabsorption and ? water
  excretion

Dopamine dilates afferent and efferent arterioles
(via D1 receptor activation) ? Low dose
dopamine partially reverses norepinephrine
induced renal vasoconstriction ? Dopamine ? PCT
Na reabsorption
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• Autoregulation impaired in
• Severe sepsis
• ARF
• During cardiopulmonary bypass
• Autoregulation is not abolished by most
  anaesthetic agents

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Tubule

• Proximal Tubule (PCT)
• 60-75 ultrafiltrate ? reabsorb isotonically in
  PCT
• To be reabsorbed most substances have to pass
  through apical side of cell membrane ?
  basolateral cell membrane ? renal interstitium ?
  peritubular capillaries
• Carbonic anhydrase inhibitors (acetazolamide)
  interfere with Na reabsorption and H secretion
  in PCT

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Pump mechanisms of tubule
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• Functions
• Reabsorption
• NaCl
• Water
• Bicarbonate
• Glucose
• Proteins
• Aminoacids
• K, Mg, PO4, uric acid, urea
• Secretion
• Organic anions
• Organic cations
• Ammonia products

Reabsorption of solutes in PCT
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• Sodium reabsorption in PCT (65-75 of filtered
  Na load reabsorbed)
• Na is actively transported out of PCT cells at
  their capillary sides by membrane bound Na K
  ATPase
• ?
• Resulting low intracellular concentration of Na
• ?
• Passive movement of K down its gradient from
  tubular fluid into epithelial cells
• ?
• Na reabsorption is coupled with reabsorption of
  other solutes ? and secretion of H ?
  reabsorption of 90 of filtered HCO3 ions
• Chloride absorption ? passive ? follows
  concentration gradient ? transverse tight
  junctions between adjacent tubular epithelium

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• Water ? specialised channels composed of membrane
  protein aquaporin-1 (apical membrane) ?
  facilitate water movement passively along osmotic
  gradients
• Secretion
• Cations ( Creatinine, cimetidine, quinidine,)
  share same pump mechanism and interfere in
  excretion of one another
• Anions include Urate, ketoacids, penicillins,
  cephalosposins, diuretics, salicyclates and most
  x-ray dyes

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• Loop of Henle
• 25-30 ultrafiltrate reaches loop of Henle
• ?
• 15-20 filtered Na load reabsorbed
• Solute and water reabsorption is passive and
  follows concentration and osmotic gradients
  (except thick ascending loop)
• Ascending thick segment
• Sodium reabsorption is coupled to both K and Cl-
  reabsorption
• Cl- in tubular fluid is rate limiting factor
• Important site for calcium and magnesium
  reabsorption
• Parathyroid hormone ? calcium reabsorption at
  this site
• Loop diuretics inhibit Na and Cl reabsorption in
  TAL compete with Cl- for its binding site on
  carrier protein

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Sodium and chloride reabsorption in thick
ascending loop
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• Counter current multiplier (loop of Henle)
• Counter current multiplier exchangers (cortical
  and medullary collecting tubules and their
  respective capillaries - vasa recta)

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• Tubular fluid enters the distal PCT iso-osmotic
  with plasma (300 mOsm/kg) (1).
• Descending limb of Henle (2) ? water rapidly
  diffuses out into the increasingly hypertonic
  medulla and is removed by the vasa recta
• Tubular fluid becomes hypertonic, largely because
  of conc. of NaCl.
• Urea diffuses in from the hypertonic
  interstitium, further increasing tubular fluid
  osmolality (1200 mOsm/kg).
• Thin ascending loop of Henle (3), NaCl passively
  diffuses into the interstitium along its
  concentration gradient
• But water is trapped in the water-impermeable
  tubule, which progressively decreases tubular
  fluid osmolality.
• Urea passively diffuses into the tubular fluid
  (urea recycling).
• Tubular dilution is accelerated by active
  reabsorption of NaCl in the thick ascending loop
  and proximal distal tubule (4).

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• Fluid entering distal tubule is quite
  hypo-osmotic (100 mOsm/kg)
• In the collecting segment (5), the osmolality of
  the tubular fluid returns to that of plasma (300
  mOsm/kg)
• But contents of the proximal tubule, the solute
  component consists largely of urea, creatinine,
  and other excreted compounds.
• Increased plasma antidiuretic hormone (ADH)
  renders the cortical and medullary collecting
  ducts (6) permeable to water, which passively
  diffuses into the hypertonic medullary
  interstitium.
• Some urea diffuses out into the medulla, the
  maximal osmolality of concentrated urine (7)
  approaches that of the hypertonic medullary
  interstitium, about 1200 mOsm/kg
• In the absence of ADH, the collecting ducts
  remain impermeable to water, and the urine is
  diluted.

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Counter current multiplier
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Counter current exchange by vasa recta
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• Distal tubule
• Very tight junctions between tubular cells
  relatively impermeable to water and Na
• 5 of filtered Na load ? reabsorbed
• Major site of parathyroid hormone and vit D
  mediated calcium reabsorption
• The late distal segment (collecting segment)
• Hormone mediated Ca reabsorption
• Aldosterone mediated Na reabsorption

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• Collecting tubule
• 5-7 of filtered Na load is reabsorbed
• Cortical collecting tubule two types of cells
• Principal cells ? secrete K aldosterone mediated
  Na reabsorption
• Intercalated cells ? acid base regulation

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Secretion of hydrogen and reabsorption of
bicarbonate and potassium in cortical collecting
tubule
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• Aldosterone
• Enhances Na K ATPase activity by ? number of
  open Na K channels in luminal membrane
• Enhances H secreting ATPase on the luminal
  border od intercalated cells
• Because principal cells reabsorb Na via an
  electrogenic pump
• Either Cl- must be reabsorbed
• K must be secreted to maintain electroneutrality
• ? intracellular K favours K secretion

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• K sparing diuretics
• Competitive
• Spironolactone aldosterone receptor antagonist
• Inhibits aldosterone mediated sodium reabsorption
  and potassium secretion in collecting tubule
• Non-competitive
• Triamterene and amiloride inhibits sodium
  reabsorption and potassium secretion by
  decreasing number of open channels in luminal
  membrane of collecting tubule

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• Medullary collecting tubule
• Site of actiion of ADH or AVP (arginine
  vasopressin) ? activates adenylate cyclase
• Dehydration ? ? ADH secretion ? luminal membrane
  becomes permeable to water ? water is osmotically
  drawn out of tubular fluid passing through the
  medulla ? concentrated urine (upto 1400 mos)
• Adequate hydration suppressed ADH secretion ?
  fluid in collecting tubule passes through medulla
  unchanged and remains hypotonic (100-200 msom/l)
• Hydrogen ion secreted are excreted in the form of
  titrable acids (phosphates) and ammonium ions

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References

• Millers Anaesthesia, 6th ed. Functional anatomy
  and renal physiology.
• Wylie and Churchill Davidsons. Functional
  anatomy and renal physiology, 7th ed.
• Barash Clinical Anaesthesia, Functional anatomy
  and renal physiology, 5th ed.
• Morgan. Clinical Anaesthesiology, 4th ed.
• Ganong WF. Review of Medical Physiology, 20th ed.

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Thank You