Body fluids and Renal function

Question 1

The kidneys primary role is that of water and electolyte homeostasis together with waste excretion.

What are the numerous other homeostatic functnios performed by the kidney?

Answer 1

• Regulation of arterial blood pressure
  
  • Primarily through activation of the RAAS
• Regulation of acid-base balance
  
  • Control of hydrogen ion and HCO₃^- excretion
• Regulation of red blood cell production
  
  • Production of EPO
• Secretion, metabolism and excretion of various hormones
  
  • Especially formation of 1, 25-dihydroxyvitamin D₃ (calcitriol)
• Gluconeogenesis

Question 2

What are the major wast products excreted by the kidneys, and from where are they derived?

Answer 2

• Urea
  
  • From amino acid breakdown
• Creatinine
  
  • From muscle phosphocreatine
• Uric acid
  
  • From nucleic acid metabolism
• End products of haemoglobin breakdown
• Metabolites of various hormones

Also responsible for elimination of the majority of toxins and foreign substances that are ingested by the body

Question 3

Describe the innervation of the bladder

Answer 3

• Principle nerve supply via the pelvic nerves
  
  • Segments S2-S3 of the spinal cord
  • Sensory and motor fibres present
    
    • Sensory nerves detect stretch in the bladder neck
    • Motor nerves - parasympathetic and innervate the detrusor muscle and internal urethral sphincter
• Pudendal nerve
  
  • Arises from the S2-S3 segment of the spinal cord
  • Innervates skeletal muscle fibres in the external urethral sphincter
  • Somatic nerve fibres innervating voluntary skeletal muscle
• Hypogastric nerve
  
  • Sympathetic nerve arising from L1-L4
  • NE neurotransmitter
  • Acts on beta receptors on the detrusor muscle (relaxation when active)
  • Acts on alpha receptors in the internal urethral sphincter (contraction when active)

Question 4

Describe the neurological pathway that initiates and controls micturition

Answer 4

1. The bladder fills to a critical point - bladder filling is sensed by the afferents in the pelvic nerve (parasympathetic)
2. The signal transmitter by the pelvic nerve travels up the spinal cord to the micturition centre in the pontine micturition centre
3. Signals transmit between the pons and the cerebral cortex and hypothalamus to enact voluntary control
4. If appropriate, signals are sent via the parasympathetic (pelvic) nerve to initiate detrusor contraction via ACh release
5. Simultaneously, inhibitory signals reduce sympathetic tone allowing appropriate detrusor contraction and causing relaxation of the urethral sphincter

Question 5

Describe the filtration unit of the kidney, the glomerulus

Answer 5

• Tuft of capillaries supplied by the afferent arteriole
• The filter is made up of:
  
  • The capillary endothelium
  • The basement membrane
  • A layer of epithelial cells surrounding the BM
    
    • Podocytes
• Thousands of fenetrations in the endothelium
• Negative charge of the endothelium helps limit protein filtration
• BM: loos connective tissue (collagen) and proteoglycan network - also negatively charged
• Podocytes are separates by slit pores and also negatively charged

Question 6

List the glomerular diseases that have been documented in dogs and cats

Answer 6

1. Membranous nephropathy
2. Membranoproliferative glomerulonephritis
3. Proliferative glomerulonephritis
4. Imunoglobulin A nephropathy
5. Amyloidosis
6. Hereditary Nephritis
7. Minimal change disease
8. Glomerulosclerosis

Question 7

Describe the various pathophysiologcal processes that cause the different glomerular diseases

Answer 7

1. Immune complex formation and deposition
   
   • eg. subendothelial side of the basement membrane in membranoproliferative glomerulonephriti s
   • Binding of antibodies to the subepithelial side in membranous nephropathy
   • Anti-glomerular basement membrane complexes
     
     • Described in humans with proliferative glomerulonephritis
2. Proliferation of the endocapillary or mesangium
   
   • Described for proliferative glomerulonephritis and immunoglobulin A nephropathy
3. Amyloidosis
   
   • Protein deposits are seen primarily within the glomerulus, except in the Shar Pei and Abyssinian (renal medulla)
4. Inherited collagen type IV defects
   
   • Early deterioration of the basement membrane (which is primarily composed of type IV collagen)
     
     • Seen in hereditary nephritis in English Cocker Spaniel, dalmation, Springer Spaniels and Bull Terrier. X-linked form in Samoyed dogs
5. Minimal change disease - triggered by increased production of lymphokines by dysfunctional T cells
   
   • loss of negative charge alters podocyte foot process
   • selective loss of albumin
6. Glomerulosclerosis - thickening/scarring of the glomeurlar capillies. Tends to be segmental / focal

Question 8

Describe the process whereby increased glomerular filtration of protein causes tubulointerstitial cell damage

Answer 8

• Increased protein can be filtered by the glomerulus ddue to numerous different underlying mechanisms
• Increased protein (less so albumin) within the renal tubules needs to be resorbed by the proximal tubules
• The process of protein resorption increases the workload of the tubular epithelial cells
• The proteins can be cytotoxic
  
  • The combination of cell damage and increased cell workload can lead to cell death
• Protein casts can slow tubular flow and cause obstruction and increased tubular pressures
• Glomerular injury can lead to reduced perfusion of the tubular region due to reduced blood flow from the efferent arteriole

Question 9

Describe how GFR can be altered

Answer 9

• Glomerular blood flow can be increased by either
  
  • Increasing cardiac output
  • Decreasing arteriolar tone (reducing hydrostatic pressure)
• GFR can be reduced by:
  
  • Increases in Bowman’s capsule hydrostatic pressure
  • Reduced cardiac output
  • Increased afferent arteriolar tone
  • Increased glomerular capillary colloid osmotic pressure

Question 10

Briefly list and describe the effects various hormones that can impact renal blood flow

Answer 10

• Epinephrine and norepinephrine
  
  • Parallel the effects of the sympathetic nervous system
  • Vasoconstriction effects largely balanced by autoregulatory effects at the tissue level
• Endothelin
  
  • Potent vasoconstrictor that is released in response to vascular injury
    
    • Also released / increased in certain disease states
• Angiotensin II
  
  • Mostly constricts the efferent arteriole
    
    • Afferent is relatively protected by prostaglandins and nitric oxide
    • Increases glomerular hydrostatic pressure while reducing renal blood flow
    • Helps preserve GFR during periods of low arterial pressure
    • Low blood flow in the peritubular capillaries helps to increase sodium and water resorption
• Nitric Oxide
  
  • Potent vasodilator helps to maintain renal blood flow and therefore GFR
• Prostaglandins and bradykinin
  
  • Vasodilatory effect on arterioles - especially on the afferent arteriole
  • Help to counter the effects of SNS and AT II

Question 11

What is the purpose and drive of tubuloglomerular feedback?

Answer 11

• Tubuloglomerular feedback helps link changes in sodium concentration in the distal tubules to renal arteriolar blood flow, autoregulation and GFR
• This feedback loop helps to deliver a constant flow of sodium chloride to the distal tubule preventing spurious fluctuations that would otherwise occur

Question 12

Describe the tubuloglomerular feedback mechanism

Answer 12

• The mechanism has two components that work together to control GFR
  
  • Afferent feedback mechanism
  • Efferent feedback mechanism
• The juxtaglomerular complex consists of the macula densa cells within the proximal portion of the distal convoluted tubule and JG cells in the walls of the afferent and efferent arterioles
  
  • The macula densa cells have secretory vescicles that are directed towards the arteriolar walls
• Decrease macular densa NaCl causes dilation of the afferent arterioles and increased secretion of renin
  
  • Decreased NaCl at this site occurs with increased NaCl resorption in the loop of Henle due to reduced flow rate

1. Increased flow at the afferent arteriole increases GFR
2. Renin → AT II → efferent arteriole constriction → increased GFR

*

Question 13

Describe the physiological mechanism as to why high protein intake and hyperglycaemia increase renal blood flow and GFR

Answer 13

• Protein is digested to release amino acids into the circulation.
• Amino acids and glucose are both resorbed from the proximal renal tubules back into the blood stream
  
  • This transport occurs in conjunction with sodium
  • Increased AA or glucose absorption also increases sodium resorption
• This leads to less sodium in the ascending loop of Henle and at the macula densa
• Low sodium is detected at this site and tubuloglomerular feedback leads to arteriolar dilatation, increase in renal blood flow and GFR

Question 14

List six situations / conditions in which renal blood flow and glomerular filtration are increased

Answer 14

1. High salt diet
2. High protein diet
3. Diabetes mellitus
4. Obesity - early prior to potential renal damage
5. Glucocorticoid excess (endogenous or exogenous)
6. Fever - due to circulating pyrogens

Question 15

Describe the process of active transport required for sodium resorption in the renal tubule

Answer 15

• Na/K ATPase pumps sodium from the cell into the interstitial space.
  
  • 3 sodium out of the cell, 2 potassium into the cell
  • Sodium is maintained at a high concentration in the interstitium and can diffuse back into the peritubular capillary
• This process creates a low sodium concentration and a negative within the tubular cell
• High sodium concentration in the tubular fluid can then diffuse passively into the tubular cell
• In the proximal convoluted tubule, a dense brush border increases the luminal side surface area by ~ 20 fold
  
  • Carrier proteins in the proximal convoluted tubule also allow for facilitated diffusion of sodium at this site
    
    • This is important for secondary active transport of amino acids and glucose

Question 16

Describe the processes that cause paradoxical aciduria with gastric outflow tract obstruction

Answer 16

• GOO causes vomiting and subsequent loss of chloride and acid together with total water volume
• The result is dehydration with hypochloraemia and a metabolic alkalosis
• Reduced blood flow in the afferent arteriole ⇒ reduced GFR if not for increased renin release.
• Increased renin ⇒ increased angiotensin II and aldosterone
• Aldosterone and dehydration drive sodium resorption to help improve ECV and BP
• Active transport and counter transport of sodium occurs with Na exchanged for hydrogen ions in the proximal tubule
  
  • Sodium concentration and water volume are maintained at the expense of acid loss
• Total effect - hypochloraemic metabolic alkalosis with excess H+ ions in the urine - paradoxical aciduria

Question 17

Describe the processes that allow absorption and / or secretion in the proximal tubule

Answer 17

• Sodium
  
  • active transport down a concentration gradient
  • Concentration gradient is maintained by the Na/K ATPase pump on the basolateral membrane
• Glucose
  
  • Secondary active transport via the SGLT (sodium glucose transported into the tubular cell
  • Pumped out of the cell via the GLUT into the interstitial space at the basolateral membrane
• Phosphate
  
  • Secondary active transport via sodium dependent P(i) cotransporters
  • Regulated by fibroplast growth factor-23 (FGF23)
    
    • Increased PTH and FGF23 both decrease the resorption of phosphate by the cotransporters
• Amino acids
  
  • Secondary active transport by sodium dependent SLT5 (solute carrier family protein)
• Free water - absorbed via osmosis and coupled to sodium transport

Question 18

Describe the processes that allow absorption and / or secretion in the loop of Henle

Answer 18

Descending Limb:

• Water:
  
  • resorption primarily via aquaporin channels
  • Helps to deliver a concentrated urine to the ascending limb for solute resorption

Thick Ascending Limb

• Sodium:
  
  • Co-transport with chloride and potassium via the NKCC2 symporter
• Potassium - via NKCC2 symported
  
  • Potassium also leaks back into the lumen contributing to a mild positive charge of the luminal fluid
  • This positive charge helps for drive cations out of the lumen into the cells (calcium, magnesium)
• Chloride - via NKCC2 symported
• Nodium and hydrogen counter-current exchange
• Relatively impermeable to water
• Calcium, bicarbonate and magnesium also resporbed
• • As the above electrolytes are removed, the urine becomes more dilute
• Delivers luminal fluid to the macula densa where the sodium concentration is sensed

Question 19

Describe the processes that allow absorption and / or secretion in the distal convoluted tubule

Answer 19

• Sodium
  
  • Na⁺K⁺ ATPase pump continues to maintain a concentration gradient
  • Sodium diffuses down the concentration gradient primarily via the NCC cotransporter
• Chloride
  
  • Primarily reabsorbed together with sodium via the NCC
  • Chloride channels in the basolateral membrane allow for diffusion out of the cell
• Calcium
• Magnesium

Question 20

Describe the processes that allow absorption and / or secretion in the late distal convoluted tubule and collecting ducts

Answer 20

• Principle cells
  
  • Resorb sodium in exchange for potassium
  • K+ gradient is generated by the Na⁺K⁺ ATPase pump in the basolateral membrane
    
    • Site of action of aldosterone and therefore the aldosterone receptor blocker spironolactone
  • K+ leaves the cell into the duct lumen down a concentration gradient via K⁺ channels
  • Na resorption from the lumen via Na⁺ channels
• Intercalated cells
  
  • Major role in acid base regulation
  • H+ secreted in type A cells via:
    
    • H⁺-ATPase (against large concentration gradient) and H⁺Na⁺ exchanger
    • These cells produce bicarbonate for resorption
  • Type A cells resorb potassium and excrete chloride
  • Type B cells
    
    • Chloride bicarbonate counter-transporter secretes bicarbonate
    • Resorb chloride and secrete potassium
• Water resorption is controlled largely by ADH regulation of aquaporin channels

Question 21

List the various mechanisms by which tubular resorption can be controlled

Answer 21

1. Glomerulotubular balance
   
   • Increased GFR - increased tubular resorption
2. Peritubular capillary and renal interstitial forces
   
   • Changes in capillary hydrostatic pressure can influence hydrostatic and osmotic pressure in the interstitium
3. Arterial pressure
   
   • Effects urine output by pressure diuresis and pressure natriuresis
4. Hormonal control
   
   • Aldosterone promotes sodium resorption and potassium excretion
   • Angiotensin II increases sodium and water retention
   • ADH increases water resorption
   • ANP decreases sodium and water resorption
   • Parathyroid hormone increases calcium resorption
   • FGF23 increases phosphorus reabsorption, decreases calcium reabsorption
5. Sympathetic nervous system
   
   • Increases sodium reabsorption

Question 22

Describe the mechansims by which the renal medullary concnetration gradient is established

Answer 22

1. Active transport of sodium and co-transport of potassium, chloride and other ions out of the thick ascending loop of Henle
2. Active transport of solutes from the collecting duct into the interstitium
3. Facilitated diffusion of urea from the collecting ducts into the medullary interstitium
4. Diffusion of only small volumes of water from the medullary tubules into the interstitium

Question 23

Describe how urea excretion and reabsorption contributes to the medullary concentration gradient.

Answer 23

• Urea is filtered freely at the glomeruus into the tubular fluid.
• 40-50% of the filtered urea is resabsorbed in the proximal tubule - though this movement is less than water and the actual urea concentration increases
• The loop of Henle and the distal tubules and cortical collecting duct are essentially impermeable to urea
  
  • Urea is UT-A2 secretes urea into the thin loop of Henle
• Urea can diffuse down a concentration gradient from the medullary collecting duct
  
  • Diffusion is greatly facilitated by the urea transporters UT-A1 and UT-A3.
• The urea transporters are activated by ADH, increasing urea transport
• Urea moves simulataneously with water under the influence of ADH
  
  • This allows the final urea concentration within the urine to remain relatively constant

Question 24

What is the effect of low blood urea on the renal medullary concentration gradient and urine concentration?

Answer 24

• With low blood urea from what ever cause, there is less net movement of urea from the medullary collecting into the medullary interstitium.
• As urea contributes ~40-50% of the osmolarity to the interstitium, less urea means the a smaller concentration gradient in the loop of Henle
• The smaller concentration gradient means water resorption is reduced
• Reduced water resorption leads to a lower USG and increased urine production to continue excretion of solutes such as sodium at a constant rate

Question 25

Briefly describe the process of the osmoreceptor-ADH feedback system to changes in plasma osmolarity

Answer 25

* Osmoreceptors in the anterior hypothalamus shrink slightly with increases plasma osmolarity (~increased sodium) * The osmoreceptors fire nerve signals to the supraoptic nuclei * These messages are relayed to the posterior pituitary gland * ADH is released from secretory vesicles in the posterior pituitary * ADH circulates in the blood to the kidney * Causes vasoconstriction also * ADH stimulates increased expressioin of the aquaporin channel in the distal convoluted tubule, cortical collecting tubules and medullary collecting duct * Increased free water resorption * Concnurrent increased urea resorption to increased the medullary concentrating gradient * Increased water resorption - low urine output - highly concentrated urine

Question 26

List and describe the major stimulators of thirst

Answer 26

1. Increase plasma osmolarity * Causes intracellular deydration (cell shrinkage) of osmoreceptors in the thirst centres of the brain 2. Decreased arterial blood pressure / extracellular fluid volume * Likely due to neural inputs from the baroreceptors 3. Angiotensin II * This peptide directly stimulates regions of the thirst centre 4. Dry mouth 5. Gastrointestinal and pharyngeal stimuli influence thirst * Predominantly these stimuli limit thirst - partial relief occurs with stimuli of the pharynx and stomach after drinking. This helps to temper the thirst response and minimise the risk of over-hydration

Question 27

Briefly explain the relative importance of the ADH-thirst response and the Angiotensin II - Aldosterone system for maintenance of extracellular fluid osmolarity

Answer 27

* ADH/thirst mechanisms directly affect the quantity of free water absorbed or reabsorbed into the body * This occurs either via the kidney or GIT respectively * The addition or reabsorption of free water into the extracellular fluid via both of these mechanisms has a marked and rapid effect on the concentration of solutes within this space - ie. direct effect on the osmolarity * Angiotensin II can directly impact the thirst centre * However, the majority of the effect of AT II and aldosterone is to improve or enhance sodium reabsorption in the kidney (especially the distal convoluted tubule). * Sodium reabsorption in the kidney also leads to water reabsorption via osmosis * Thus, these hormones cause an increase in extracellular fluid volume with minimal change to the sodium concentration * Minimal effect on the osmolarity

Question 28

Describe briefly how hypoaldosteronism leads to decreased plasma sodium

Answer 28

* Aldosterone helps to uprgulate the action of the Na⁺K⁺ATPase pump in the distal convoluted tubule. * The action of this pump helps to maintain a sodium concentration gradient between the tubular fluid and intracellular fluid promoting movement of sodium from the tubular fluid into the tubular cells down a concentration gradient. * ie. aldosterone helps enhance sodium reabsorption * Is sodium is not reabsorbed, then both sodium and water are lost in the urine * Dehydration is initially accompanied by normo-osmolar plasma and extracellular fluid * This fluid loss leads to stimulation of the thirst centre and replacement of ECF loss with free water * Ongoing loss of sodium, replaced by free water eventually reduces the plasma and ECF osmolarity * Reduced sodium can further lead to reduced urine concentration and increased free water loss due to a reduction in the medullary concentration gradient

Question 29

List the various machanisms or situations by which potassium will move between the extracellular and intracellular fluid compartments

Answer 29

Potassium moves into the cellular fluid compartment: * Insulin * Aldosterone * b-adrenergic stimulation * Alkalosis Potassium moves into the extracellular fluid compartment with the opposite of the above: Lack of insulin or aldosterone and b-adrenergic blockade together with acidosis.

Question 30

Briefly overview the excretion of potassium as it passes through the kidney (nephron)

Answer 30

* Renal potassium excretion is determined by the GFR and the rate of both potassium reabsorption and secretion within the tubules * GFR and filtration is relatively constant in a healthy animal * 65% of filtered potassium is reabsorbed in the proximal tubule * 25-30% is reabsorbed in the loop of Henle (especially the thick ascending limb) - via NKCC2 symporter * The collecting tubules can reabsorb or secrete potassium and are responsible for the majority of excretion control based on daily potassium intake * Excretion driven by action of the Na⁺K⁺ATPase in the principle cells * Potassium moves out into the tubular fluid via the "big potassium channel" and the ROMK (renal outer medullary potassium channel) * The type A intercalated cells reabsorb potassium in exchange for chloride

Question 31

Describe the 4 major mechanisms that help to stimulate potassium secretion during a period of hyperkalaemia or with increased potassium intake

Answer 31

1. Increased activity of the Na⁺K⁺ATPase pump inthe distal tubule * Increases potassium uptake into the cell increases the diffusion gradient into the luminal fluid 2. Increased ECF potassium reduces the backleak of potassium from the cells into the ECF 3. Increased synthesis of potassium channels in the luminal membrane - ROMK and big potassium channels 4. Increased aldosterone secretion - upregulates the action of the Na⁺K⁺ATPase pump which facilitates movement of potassium into the cell and down the diffusion gradient as in 1.

Question 32

Describe how acidosis and alkalosis effect potassium secretion

Answer 32

* Acidosis leads to an increase in hydrogen ion buildup in the interstitial space and cellular fluid * H+ is exchanged for potassium via the H⁺K⁺ATPase in the luminal membrane of the type A intercalated cell. * Increased acid therefore leads to exchange with potassium and increased reabsorption of K⁺ * Acidosis also inhibits the Na⁺K⁺ATPase in the basolateral membrane * Reduced intracellular potassium increases the diffusion gradient from the luminal fluid into the cell

Question 33

Describe the processes of renal calcium filtration and reabsorption

Answer 33

* Calcium is ~40% bound to protein and ~10% bound to phosphate and citrate * ~50% of the plasma calcium is ionised free calcium * Only ionized calcium is filtered at the glomerulus * ~65% is filtered at the proximal tubule, predominantly via the paracellular route dissolved in water * ~20% diffuses through the cell down an electrochemical gradient * Exits the basolateral membrane via Ca⁺⁺ATPase pump and by sodium-calcium counter transport * Thick ascending limb - 50% resorbed via the paracellular route * 50% via transcellular route - mediated by PTH * Distal tubule - PTH mediated active transcellular transport

Question 34

Describe the action of PTH on renal calcium resorption / secretion

Answer 34

* Plasma calcium concentration is sensed by the *calcium-sensing receptors* on the parathyroid gland * Increased calcium - increased CSR activity - decrease PTH release * Decreased calcium - decreased CSR activity - increased PTH release * Increased PTH stimulates increased calcium reabsorption primarily in the distal convoluted tubule * PTH regulates expression and function of two proteins responsible for transcellular calcium transport

Question 35

Briefly describe the renal control mechanisms that can affect the reabsoprtion or exretion of phosphate

Answer 35

* The rate of phosphate excretion is largely controlled by a spill-over mechanism. * Basically: Increased serum phosphate is filtered at the glomerulus and once the threshold for resorption is reached, the remainder is excreted in the urine * The proximal tubule resorbs 75-80% of filtered phosphate * Primarily via co-transport with sodium from the lumen * The distal tubule resorbes ~ 10% of the filtered phosphate * ~ 10% of filtered phosphate is excreted in the urine * PTH decreases the expression of the sodium-phosphate co-transporter in the apical membrane * FGF23 triggers internalisation and degradation of the sodium-phosphate co-transporter - reduces phosphate reabsorption. * Also reduces vitamin D synthesis, thereby reducing phosphorus absorption in the gut.

Question 37

List the various diuretics and their respective site/method of action

Answer 37

1. Osmotic diuretics: eg. mannitol * filtered by the glomerulus but not resorbed in the tubules. Acts to draw water into the tubules or at least prevent reabsorption 2. Loop diuretics: eg. frusemide * Blocks the NKCC2 co-transporter. Increases solute delivery to the distal convoluted tubule - maintains osmotic gradient within the luminal fluid. Impairs countercurrent exchange in the loop of Henle 3. Thiazide diuretics: eg. hydrochlorothiazide * NaCl cotransporter blockade * Reduces Na+ resorption in the distal convoluted tubule 4. Carbonic anhydrase inhibitors: eg. acetazolamide * Blocks conversion of CO₂ and H₂0 to H⁺ and bicarbonate especially in the proximal tubules * Reduces H⁺ exchange for sodium in the distal tubules * Redcued bicarbonate and sodium reabsorption * Subsequent acidosis 5. Aldosterone receptor antagonists: eg. spironolactone * Block effect of aldosterone on the Na⁺K⁺ATPase pump and potassium channels 6. Sodium channel blockers: eg. triamterene * Blocks the sodium channel in the collecting tubules * Subsequent decrease in Na⁺K⁺ATPase activity and reduced potassium excretion

Question 38

Describe the major physiological effects of an acute kidney injury

Answer 38

* Marked reduction in renal blood flow and glomerular filtration rate * Reduced GFR: * Reduced excretion of waste products such as urea / creatinine * Inability to excrete solutes such as sodium, potassium and hydrogen ions * Impaired ability to excrete water * Retention of solutes and water leads to volume / fluid overload and hypertension * Increased potassium reduces membrane excitability * Inability to remove acid can aggravate hyperkalemia

Question 39

What is the basic cause for a loss of renal concentrating ability due to pyelonephritis?

Answer 39

* Pyelonephritis can be caused by the blood stream, but is more often caused by ascending infection for the bladder * This is allowed due to vesicoureteral reflux duringh micturition * Infection (often E coli) invades the renal pelvis initially * The localisation within the renal pelvis and calyxes leads to medullary inflammation * Medullary inflammation can markedly affect the countercurrent mechanism for concentrating urine in both the loop of Henle and the collecting ducts * This leads to a marked reduction in concentrating ability

Question 40

Why may azotemia not be seen with early pyelonephritis?

Answer 40

* As the infection initially involed the medulla, there is no affect on the function of the glomerulus and cortical tubules * Filtration of the blood occurs normal and the normal portion of the urea is reabsorbed at the proximal tubules * Recycling of urea is reduced, leading to more dilute urine. * Increased urine output offsets the reduction in urea concentration * Creatinine is freely filtered and secreted into the proximal tubules. As creatinine is not reabsorbed from the tubules, creatinine levels remain normal unless there is damage to the proximal tubular or glomerular function