Renal structure and function 2 Flashcards
What are the different types of nephrons?
- Cortical
- Juxtamedullar
What is the difference between the 2 types of nephrons?
- Cortical have loops of Henle in renal medulla near junction with renal cortex
- Juxtamedullary have their loops of Henle deep in renal medulla (glomeruli close to medulla but still in cortex)
What is the vascular arrangement of cortical nephrons?
Peritubular capillaries
What is the vascular arrangement of the juxtamedullary nephrons?
Have the vasa recta
Which of the nephrons concentrate the urine?
Juxtamedullary nephrons
What is the function of the loop of Henle?
Confer ability to produce concentrated urine
What is the permeability of the descending limb of the Loop of Henle?
- Permeable to water
- Via aquaporin-1
What is the permeability of the ascending limb of the Loop of Henle?
- Permable to solutes
- Impermeable to water
If an animal is dehydrated but is producing iso-osmolar urine what does this suggest and why?
- Proximal tubule carries out bulk removal of volume so start of loop of iso-osmotic
- If there is no change to the urine but animal is dehydrated, suggests kidney failure
- Not concentrating the urine even though is dehydrated
Give a general overview of the movement of solutes and water through the Loop of Henle
- Descending limb pumping out water (aquaporin-1), pumping out water -> hypertonic at end of loop
- Ascending limb impermeable to water, pumping out solutes, becomes dilute again
- Generates gradient in the interstitium
What is the tonicity of the medullary interstitium and how is this acheived?
- Hypertonic
- Countercurrent multiplier and countercurrent exchange, maintained by vasa recta
Describe the countercurrent multiplier system in the Loop of Henle
- Descending loop permeable to water, not solutes
- Ascending loop permeable to solutes not water
- Interstitial osmolarity elevates as go deeper, drawing water out of descending
- Solute concentration of fluid in ascending limb higher, more ions pumped out
- Increases interstitial osmolarity more, more water drawn out of descending
- U-shaped vasa recta prevents dissipation of this gradient
Describe the countercurrent exchange in the Loop of Henle
- Descending limb of vasa recta: as descends through high osmolarity water out of capillary, NaCl in
- Ascending: up through hypotonic, solutes out, more water in
- Result is no net change in medullary gradient
What is the function of the counter current mechanism?
- Concentration then dilution as pass through loop
- Establishes vertical gradient through kidney to enable production of concentrated urine
- Provides mechanisms for producing dilute urine
Explain how urea acts to support the generation of the renal medullary concentration gradient
- Is a weak osmolite
- Requires water to be excreted
- Recycling of urea maintains medullary gradient needed for counter current multiplier
Describe the passage of urea in the collecting duct
- Nephron impermeable to urea until inner medullary portion of collecting duct
- Tubular urea more concentrated as water removed
- Lower collecting duct ura passively reabsorbed via urea transporters (ADH sensitive)
- Diffuses into interstitial fluid if necessary
What are the main water outputs in the body?
- Kidneys (main one)
- Lungs
- Faeces
- Skin
- Sweat
What are the main water inputs into the body?
- Drinking (main one)
- Metabolic water
What is body water controlled by?
- Thirst (mostly)
- ADH
- Aquaporins
What, in general, do the water control systems respond to?
Changes in ECF osmolality and changes in blood volume
What is thirst controlled by?
- Osmoreceptors in hypothalamus
- Stimulate thirst in response to concentrated ECF
- Degree of stimulus leads to modification of firing of neurons
What does urine specific gravity measure?
The weight of solids in water
What is the relationship between USG and osmolality?
- Osmolality is the number of dissolved osmoles in a kg of water
- USG and osmolality usually change in parallel
- Diverge when large and heavy molecules (e.g. glucose, proteins) are present in urine
What is hypersthenuria?
Concentrated urine - lots of solutes, not much water
What is hyposthenuria?
Dilute urine - lots of water, not many solutes
What is isosthenuria?
Same as plasma concnetration, nothing being done to the ultrafiltrate
What is suggested by persistent hyposthenuria?
- Increased loss of water without increased loss of solute
- Polyuria
- Diabetes insipidus
What is suggested by persistent hypersthenuria?
- Loss of solutes without water
- Dehydration
What is suggested by persistent isosthenuria?
- Fixed and persistent suggest no ability to dilute or concentrate urine
- Kidney failure
What is ECF volume altered by?
- Water intake
- Intravenous infusion of solutions
- Loss from GIT
- Loss from blood
- Loss from sweating
- Loss from kidneys
What is the action of ADH?
- Preserve blood volume
- Prevent diuresis
- Prevent natriuresis
- Increase blood pressure by inducing vasoconstriction
In what situations is ADH increased?
- Hypovolaemia (decreased atrial filling pressure)
- Hypotension (baroreceptor mediated)
- Dehydration (osmolarity increases)
- Angiotensin II
- Increased sympathetic innervation
How does ADH exert its action?
- Binds to receptors (V1 and V2) in cortical adn distal collecting duct
- Activates aquaporins to insert in apical membrane of principle cells
What is the function of aquaporins?
Allow rapid water transport across cell membranes
Describe the structure of aquaporins
- 4 proteins in epithelial membranes
- Hydrophilic pore to allow water through
- 2 important ones: AQP1 and AQP2
Describe aquaporin-1
- Apical and basolateral membrane of proximal tubule
- Isosmotic removal of water and solutes
- Main relevant channel in descending loop of Henle (water loss from tubule)
Describe aquaporin-2
- Main relevant channel in collecting duct that is ADH-responsive
- In presence of ADH, lots of AQP-2 insert on apical membrane
- Retention of hypotonic fluid entering cortical collecting duct
- Production of concentrated urine
How is blood volume/pressure maintained?
- ECF volume and osmolarity (Na concentration)
- Voume affectin g ADH
- ANP
- RAAS (blood pressure)
- Aldosterone (by increasing Na concentration)
What are the reference ranges for water intake, urine volume and urine osmolal for a cat?
- Water intake: 45ml/kg/day
- Urine volume: 10-28ml/kg/day
- Urine osmolal: 1.020-1.040 mosmoles
What are the reference ranges for water intake, urine volume and urine osmolal for a dog?
- Water intake: 90ml/kg/day
- Urine volume: 20-100ml/kg/day
- Urine osmolal: 1.016-1.060 mosmoles
What are the reference ranges for water intake, urine volume and urine osmolal for a sheep?
- Water intake: 6L/day
- Urine volume: 10-40ml/kg/day
- Urine osmolal: 1.015-1.045 mosmoles
What are the reference ranges for water intake, urine volume and urine osmolal for a cow?
- Water intake: 100L/day
- Urine volume: 17-45ml/kg/day
- Urine osmolal: 1.030-1.045 mosmoles
What are the reference ranges for water intake, urine volume and urine osmolal for a horse?
- Water intake: 40-50L/day
- Urine volume: 3-18ml/kg/day
- Urine osmolal: 1.025-1.060 mosmoles
Compare dehydration and hypovolaemia
- Dehydration: specific loss of just water (osmolality increased)
- Hypovolaemia: loss of blood volume (osmolality stays the same)
What may cause primary loss of Na?
- Diarrhoea
- Vomiting
- Diuretics
- Addison’s disease
What may cause excess water retention?
Increased secretion of ADH
What may cause primary loss of water?
Inability to produce ADH
What may cause excess Na in ECF?
- AME
- Increased aldosterone
- Cushing’s disease
What is the role of the kdiney in maintenance of the internal (watery) environment?
- Regulation of water, ion and pH levels
- Elimination of organic wastes and excess electrolytes
What is the endocrine function of the kidney?
- Production of erythropoeitin
- Calcitriol
- Renin
How does hydrostatic pressure relate to filtration in the glomerulus?
- higher pressure in efferent than afferent
- Increases pressure in glomerulus
- Affects podocytes and gaps between
- Hydrostatic pressure in glomerulus affects how much is pushed out
What facilitates filtration in the glomerulus?
- Fenestrated endothelium
- Glomerular basement membrane (-ve charge, thick)
- Podocytes
What is the osmolality of the ultrafiltrate?
Same as plasma
What is azotaemia?
Build up of nitrogen compounds (e.g. creatinine and urea) in the blood
What is meant by pre-renal renal disease?
Changes in body or organ that lead to changes in kdiney function e.g. hypertension
What is meant by renal renal disease?
Intrinsic problem of the kidney e.g. interstitial fibrosis
What is meant by post-renal renal disease?
Problem after the kidney affecting its function e.g. urethral bloackage, stenosis
What is the most common type of renal disease?
Pre-renal
What are teh sites of potential renal damage and what is the effect?
- Glomerular: filtration affected
- Tubular: secretion and reabsorption affected
- Interstitial: ability to concentrate urine affected
What factors determine the glomerular filtration rate in a single nephron?
- Pressure in afferent/efferent arteriole
- Colloid osmotic pressure
- Hydrostatic pressure
- Renal plasma flow
- Electrical charges across the glomerular basement membrane
What is the glomerular filtration rate?
The volume of fluid filtered from the glomerular capillaries into the Bowman’s capsule per unit time
- Sum of ultrafiltrate from both kidneys/time
What are the limitations to measuring GFR in practice?
- Inferred via serum creatinine (SCr)
- SCr influences by lean mass, breed, diet
- Low GFR indicated nephrone loss - shown by high SCr (BUN)
- Usually measured by creatinine clearance
What happens to GFR in renal damage?
- Nephron loss
- Cannot be regenerated
- Other nephrons increase in function
- But GFR will not increase again
What exerts the hydrostatic pressure?
- Water in blood
- Cardiac output generates pressure
- Afferent and efferent arterioles determine relative pressure difference across glomerulus
- Concentration of plasma proteins
What occurs in proteinuria?
- Loss of protein to urine
- Less protein in plasma
- more in tubular fluid
- Less net filtration force, less fluid filtered out of blood
- Fluid retention leading to oedema
Define renal clearance
The volume of plasma from which a substrance is completely removed by the kidney in a given amount of time (e.g. a minute)
- Is ameasure of kidney’s ability to remove compounds from teh blood
How can GFR be measured?
- Clearance of a substance
- Usually creatinine
- Also iohexol, inulin, Tc-99m (radioactive tracer, used for renal split function and in larger animals)
Why can creatinine clearance be used as a measure of GFR?
- Is not reabsored or secreted by the kidney
- Small and free of charge
- What ends up in the urine is exactly what came from the ultrafiltrate
- The amount flowing through the nephrons is the amount being produced
What are the factors that affect renal clearance?
- GFR
- Tubular reabsorption
- Tubular secretion
How is creatinine clearance measured?
- Catheterise bladder, remove all urine
- Collect all urine over given time (e.g. 24 hours)
- Collect blood sample in middle of this time period
- At end, measure Cr in urine
- Measure Cr concentration in blood
- Compare
Where does creatinine come from?
- Creatinine phosphate in muscle
- Produced at a fairly constant rate by the body
- Produced daily and is related to muscle mass
What is creatinine?
A non-protein nitrogenous substance from muscle
What information does the ratio of urine to serum creatinine provide?
- Indirect information about glomerular filtration and tubular function
What is involved in sedimentary analysis of urine?
- RBC
- WBC
- Epithelial cells
- Micro-organisms
- Crystals (type, concentration, pH, some found in normal urine)
- Casts (should be none)
What is the role of the kidney in regulation of acid base balance?
- Second biggest control of acid-base after lungs
- Excretes hydrogen ions to maintain constatn concentration of H+ in the body
What are the mechanisms of H+ excretion in the kidney?
- Na/H exchange in proximal tubule
- Active H+ ATPase pymp in collecting ducts
Why must H+ be excreted?
- Very reactive
- Reacts with proteins easily even when found at 1 millionth concentration of other electrolytes
- Avoid detrimental changes in proteins, enzyme structure, cellular structure
What is the primary physiological regulator of acid secretion?
Extracellular pH
How is H+ excreted by the kidneys?
- Must be bound to filtered buffers such as phosphate or ammonia
- Too reactive to be excreted on its own
- Na/H exchange in PT, H+ ATPase pump in collecting ducts
What are the 4 major factors which control bicarbonate reabsorption?
- Luminal HCO3- concentration
- Luminal flow rate
- Arterial pCO2
- Angiotensin (via decrease in cyclic AMP, alters flow
through kidney) - Increase in each of the above will increase bicarb reabsorption
What is the importance of carbonic anhydrase in bicarbonate reabsorption?
- Allows continuous bicarbonate reabsorption by generating the bicarb from H2O and CO2, making a concentration gradient and also producing H+ ions to be secreted
Where does the energy for proximal acidification come from?
Basolateral Na/K ATPase pump
Describe the process of bicarbonate reabsorption in the proximal tubule
- HCO3- cannot cross apical membrane of PCT cell
- Binds to secreted H+ to produce CO2 and H2O which can cross membrane
- Converted to H+ and HCO3- using carbonic anhydrase
- HCO3- crosses basolateral membrane ia Na+/HCO3- symporter
- 3 bicarb per 1 Na+
What is the importance of the basolateral Na/K ATPase pumps in the proximal tubule?
- Provide energy for proximal acidification
- Are electrogenic in opposite direction to Na/HCO3- symporter
- Sodium pump keeps intracellular Na+ low, setting up gradient for H+/Na+ antiport on apical membrane
What is the main role of distal tubule acidification?
Primary role in minimising K+ loss
How does distal tubule acidification occur?
H+ secreteion in cortical and medullary collecting tubules by active secretion using H+ATPase
What is the role of filtered weak acids as buffers?
- Bicarbonate buffer is open system (primary buffer of ECF)
- Buffers of H+ in urine
What is a buffer?
A compound that can accept or donate protons (H+) to minimise change in pH
What is the role of ammonium in the renal tubular cells?
- H+ can be excreted as ammonium
- Adds flexibility to renal acid base regulation (by regulating NH4+ production)
- As more is used, more is made
How is ammonium produced in the renal tubular cells?
- Glutamine from peritubular capillaries and filtrate
- Glutaminase to make glutamate and ammonium
- Glutamate metabolised to produce alpha-ketoglutarate
- This metabolised to give 2 HCO3- ions and NH4+
- Also produces glucose
Where is the majority of ammonium produced in the nephron?
In the proximal convoluted tubule cells
What is ammonium cycling in the nephron and how does this occur?
- Ammonium cycled in medulla
- 75% proximally produced NH4+ removed from tubular fluid in medulla, only small amount into distal tubule
- Thick AL of LoH important for removal of NH4+
- Some interstitial NH4+ returns to late proximal tubule and enters medulla again (recycling)
How does ammonium aid H+ excretion?
- H+ excreted as part of NH4+ molecule (HCO3- produced by alpha-ketoglutarate metabolism)
- NH4+ also in equilibrium with NH3, out of cell and binds with H+ in lumen, excretion of H+ bound to NH3 (as NH4+)
What increases secretion of ammonium?
- Lower pH (i.e. higher H+ in tubular lumen)
- Increased removal of H+, extracellular pH increased to normal
What occurs to ammonium if it is returned to the blood stream?
Metabolised in liver to urea by the Krebs-Henseleit cycle
- net production of one H+ per ammonium molecule
Briefly describe ammonium excretion in the collecting ducts
- Different to proximal convoluted tubule
- Less excretion
- NH3 bids to H+ in lumen, out as NH4+
Summarise acid base regulation in the proximal tubular cell
- HCO3- and H+ being produced (carbonic anhydrase)
- 3HCO3- to blood with 1 Na (symport)
- H+ antiporter with Na: H+ into lumen, Na into cell
- H+ bound to NH3 to make NH4+ and excreted, or NH4+ directly from cell
- NH4+ produced by metabolism of alpha-ketoglutarate, also produced HCO3-
- NH4+ antiport to put Na into cell
- NH4+ in equilibrium with NH3
- NH3 out and binds to H+ for excretion
List factors that control renal hydrogen excretion
- Extracellular pH
- Plasma Cl-, K+ and PO4- concentrations
- Extracellular pCO2
- ECF volume
What is the effect of increased extracellular pH on renal hydrogen excretion?
- Increased HCO3- in blood, need to excrete HCO3- load (kidneys)
- Acute buffering (ICF and ECF)
- ## Body retains CO2 by alveolar hypoventilation (will decreases pH)
What is the effect of increased extracellular pH on Cl-, K+ and PO4-? Treatment?
- Those ions decrease
- Lactate increases
- Result is maladaptive
- HCO3- increases more
- Administer NaCl or KCl solutions
