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RENAL PHYSIOLOGYRENAL PHYSIOLOGY
LECTURE 1&2:LECTURE 1&2:
Kidney Structure, Functional RelationshipKidney Structure, Functional Relationship& Glomerular filtration& Glomerular filtration
By
DR. P MURAMBIWA
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“Kidneys are master chemists with main roles
of protecting us from pleasures of eating and
drinking, and thus their dysfunction speeds
our early death."
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OBJECTIVES 1:OBJECTIVES 1:
• Outline how body fluids are distributed.• Summarize the ionic composition of intra- and extracellular fluids.• Identify the main regions of the kidney. • Draw a labelled diagram of a nephron.• Summarize the ultrastructural features of different parts of the nephron.
• Draw a labelled diagram of the blood supply of the nephron.
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Plasma, the extracellular fluid within the vascular system
Interstitial, the extracellular fluid outside the fluid vascular system and separated
by the capillary endothelium
Transcellular the extracellular fluid separated fluids, from the plasma by an epithelial
layer and the capillary endothelium e.g., synovial fluid, fluids in the urinary tracts, aqueous & vitreous humour in the eye and cerebrospinal fluid.
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Renal Cortex
Renal Medulla
Minorcalyx
Renal PelvisRenal Artery
RenalPyramid
Renal Vein
Ureter
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Two distinct regions;
The cortex, darker outer region Medulla a pale inner region
The medulla further subdivides into conicalareas called pyramids.
RenalCortex
RenalMedulla
CorticalNephron
JuxtamedullaryNephron
osmotic gradient formation
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EfferentArteriole
Peritubularcapillaries(cortical nephrons)
VasaRecta(juxtamedullarynephrons)
collectingduct
Loop ofHenle
• The vasa recta plays a critical role in urine formation.
Blood Supplyto the Nephrons
Characteristics of the renal blood flow:
1.High blood flow.
1200 ml/min, or 20-21 % of the cardiac output. 94% to the cortex
2. Two capillary beds
High hydrostatic pressure in glomerular capillary (about 60 mmHg) and low hydrostatic pressure in peritubular capillaries (about 13 mmHg)Vesa Recta
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Why such a high blood flow?
To sustain a high rate of filtration of plasma in
the glomeruli
Blood flow is not distributed uniformly within
the kidney.
Total renal blood flow is decreased in most
stressful situations
A number of substances also affect renal blood
flow
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FUNCTIONS OF THE KIDNEYSFUNCTIONS OF THE KIDNEYS ♦ Regulation of the osmotic pressure of
the plasma and other extracellular fluids
♦ Regulation of the excretion of sodium and water and hence the volume of the extracellular fluid
♦ Regulation of individual concentrations
of many electrolytes in the extracellular fluid
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Regulation of plasma [bicarbonate] and therefore the hydrogen ion concentration
The kidneys eliminate metabolic waste
products such as urea.
They also eliminate many foreign compoundsfrom the body, including drugs such as penicillin. The kidneys produce erythropoietin, renin,
kallikrein, that leads to the formation of kinins and various prostaglandins
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♦ Kidneys have several special metabolic functions.
They are responsible for converting the inactive form of vitamin D to its active form, 1,25-dihydroxy-
vitamin D3.
The kidneys synthesize ammonia from amino acids.
The kidneys can synthesize glucose from non-carbohydrate sources.
Kidneys are sites for degradation of several polypeptide hormones, including insulin, glucagon,
and parathyroid hormone.
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OBJECTIVES 2:OBJECTIVES 2:
Define the basic processes of GFR • State the sites in the glomerulus for restriction of macromolecules
• State the determinants of GFR. • Why is renal auto-regulation important?
Summary-Processes occurring in the Nephron
Filtration
Reabsorption Secretion
Excretion
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GLOMERULAR FILTRATIONGLOMERULAR FILTRATION
• Filtration = the bulk flow of a solvent through a filter carrying with it
substances small enough to pass through the filter.
• Kidney = separation of compounds into
glomerular filtrate.
The Renal CorpuscleComposed of Glomerulus and Bowman’s capsule
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FILTRATION IN THE KIDNEYFILTRATION IN THE KIDNEY
Ultrafiltration
At the glomerulus and the Bowman’s capsule = separation of plasma water and its non-protein constituents that enter the Bowman's space.
Every minute = 125 ml of plasma is forced through the glomerular membrane into the tubule by hydrostatic pressure within the glomerulus.
Glomerular filtration barrier
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RENAL PHYSIOLOGYRENAL PHYSIOLOGY
LECTURE 1 & 2 CONT’D:LECTURE 1 & 2 CONT’D:
Kidney Structure, Functional RelationshipKidney Structure, Functional Relationship& Glomerular filtration Rate& Glomerular filtration Rate
By
DR. P MURAMBIWA
Glomerular Filtration barrier
GLOMERULAR FILTRATION RATE
• It is a bulk flow process in which water and all low molecular weight substances including small peptides move together from the glomerular capillaries into the bowman”s capsule
WHAT SUBSTANCES ARE FILTERED?
• All plasma constituents except for
• 1) high molecular weight substances such as plasma proteins like albumins and globulins i.e. those whose RMM is higher than 68 000
• 2) substances that are protein bound such as calcium and fatty acids
CONTD
• Large molecules with a net negative charge because the glomerular surface is negatively charged hence repulsion occurs i.e. proteins
• NB THE FILTRATE CONTAINS THE SAME AMOUNTS OF SUBSTANCES AS THERE ARE IN PLASMA EXCEPT FOR PROTEINS AND PROTEIN BOUND SUBSTANCES.
Forces governing GFR and RBF
FORCES INVOLVED IN GLOMERULAR FILTRATION
• Glomerular capillary pressure =60mmHg
• Fluid pressure in the bowman” s space =15mmHg
• Osmotic force due to protein in plasma =29mmHg
FORCES FAVOURING FILTRATION
• Glomerular capillary pressure
FORCES OPPOSING FILTRATION
• Fluid pressure in bowman space
• Osmotic force due to protein in plasma
NET FILTRATION PRESSURE IS POSITIVE-FAVOURS FILTRATION
CONTD
• Osmotic force due to protein higher than in all other arterioles because of loss of large quantities of water by glomerular filtration process
GLOMERULAR FILTRATION RATE
• It refers to VOLUME of fluid filtered from the glomerulus into bowman space PER UNIT TIME.
FACTORS AFFECTING GFR
• Changes in renal blood flow
• changes in glomerular capillary hydrostatic pressure due to
1) changes in systemic blood pressure2) afferent or efferent arteriolar
constriction
CONTD• Changes of hydrostatic pressure in Bowman”s
capsule due to 1) ureteral obstruction 2) edema of kidney inside tight renal capsule• changes in concentration of plasma proteins
due to 1) dehydration 2) hypoproteinaemia- however, these are minor
factors
SUMMARY OF FACTORS AFFECTING GFR
• Net filtration pressure.
• Permeability of corpuscular membrane
• Surface area available for filtration to occur
PHYSIOLOGICAL REGULATION OF GFR
• It is not fixed but regulated by1) hormones2) neural input to the 2 arterioles3) neural and hormonal input to
mesangial cells
GFR DECREASED BY
Constriction of AADilatation of EAContraction of mesangial cells that
surround the glomerular capillaries thereby reducing the surface area of capillaries available for filtration, hence at any given net filtration pressure GFR will be reduced
AGENTS CAUSING CONTRACTION OF MESANGIAL
CELLSAngiotensin IIVasopressinNor-epinephrineHistamine
AGENTS CAUSING RELAXATION OF MESANGIAL CELLS
ANPDopaminecAMP
GFR IS INCREASED BY
• Constriction of EA
• Dilatation of AA
• NB SIMULTANEOUS DILATATION AND RELAXATION OF THE 2 ARTERIOLES HAS NO NET EFFECT ON GFR
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CONCEPT OF CLEARANCECONCEPT OF CLEARANCE RBF and GFR can be measured by clearance methods.
Clearance of a substance is the volume of blood cleared of the substance in unit time.
The units of clearance are usually volume/time, (ml/min).
Renal handling of different substances
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To calculate the clearance of a substance three values must be measured.
[Substance] in plasma
=
Px
[Substance] in urine
=
Ux
Urine flow rate
=
V
Amt excreted/ min
=
Ux V
Clearance
= C= UxV ml/ time
Px
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Clearance of Na+ when given the following: PNa+
= 142 mmol/lUNa+
= 71 mmol/lV
= 1 ml/min Clearance of Na+
= 71 1
142
= 0.5 ml/min
Glomerular filtration rate (GFR) measured byclearance methods.
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GFR MEASUREMENTGFR MEASUREMENT
GFR = amount of filtrate that flows out of the renal corpuscles of both kidneys every minute.
How do we measure GFR?
Substance used must have the following properties:
freely filtered, small and must not bind to plasma protein.
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♣
must not be secreted or reabsorbed ( actively or
passively )
must not be toxic.
must not be metabolized.
The substance must be present in the filtrate at
the same concentration as in plasma.
When 99% of the filtrate is reabsorbed the
substance will remain in the tubule and excreted
in the urine.
Therefore, concentration of substance in the
filtrate = concentration of substance in the
plasma.
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MEASUREMENTMEASUREMENT WITH INULINWITH INULIN Inulin is not a normal constituent of the body.
Inulin (MW 5500) is freely transferred across the glomerular membrane in the same way as small molecules such as urea or Cl-.
Molecular weights have shown that molecular weight of 10,000 pass freely
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We need to know the following:
Urine [inulin]
( UIn ) =
60 mg/ml
Urine flow rate
(V )
=
1.1 ml/min
Plasma [inulin]
(PIn ) =
0.5 mg/ml
GFR =
UIn V = 60 x 1.1 = 132 ml/min
PIn 0.5
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Normal GFR is 125 ml/min (180 litres/day) in a normal man. Varies with body size; therefore the value is normally given as 125 ml/min/1.73 m2 body surface in young man, the body surface area is 10% less in females. GFR is low in infants and decreases in old age.
Creatinine is:
End product of muscle creatine metabolism
Used in clinical setting to measure GFR but less accurate than inulin method
Small amount secreted from the tubule
Creatinine used clinically to measure GFR
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MEASUREMENT OF RENAL BLOOD FLOW (RBF)MEASUREMENT OF RENAL BLOOD FLOW (RBF)
Using indirect methods.
substance should meet the following criteria:
totally cleared by filtration.
not reabsorbed.
not metabolized.
not toxic.
[substance] should not exceed the transport maximum
(Tm).
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Para-amminohippuric acid (PAH) is widely used to estimate RBF. [PAH] should not exceed the Tm since the substance is
eliminated from the kidney by both filtration and secretion
The amount of PAH excreted = amount of PAH filtered + the amount that is being secreted.
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AUTOREGULATION OF GFRAUTOREGULATION OF GFR
• Changes in blood pressure have little effect on RBF and GFR.
• In haemorrhage, there are increases in sympathetic nervous activity to the kidney causing vasoconstriction.
• Renal vasoconstriction is attenuated by prostaglandins.
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The most widely accepted explanation is that of the myogenic theory.
This states that " Increase in wall distension of afferent arterioles brought
about by an
increase in perfusion pressure causes automatic contraction of the smooth muscle fibres in vessel walls thereby increasing resistance to flow so keeping the flow constant despite the increase in perfusion pressure."
Mechanisms of glomerulotubular balance and tubuloglomerular feedback-Intra-renal mechanism
2934
Tubuloglomerular feedback
Myogenic mechanism of the autoregulation
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CONCEPT OF FILTRATION FRACTIONCONCEPT OF FILTRATION FRACTION
Filtration fraction= CI = 125ml/min
CPAH 600ml/min
~ 20% in normal man
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RENAL PHYSIOLOGYRENAL PHYSIOLOGY
LECTURE 3 & 4:
TRANSPORT PROCESSES IN THE PROXIMAL TRANSPORT PROCESSES IN THE PROXIMAL TUBULETUBULE
By
DR. P MURAMBIWA
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OBJECTIVES:OBJECTIVES:
1. State major characteristics of proximal-tubular system for reabsorption and secretion of electrolytes. 2. What are the pathways for sodium reabsorption across the proximal tubule epithelium? 3. Describe the renal handling of various organic and inorganic substances.
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INTRODUCTIONINTRODUCTION
The proximal tubule = a major site where many
substances are reabsorbed such as :
Na+
Cl-
H2O
HCO3-
Glucose
Amino acids
Urea
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REABSORPTION AND SECRETIONREABSORPTION AND SECRETION
• Indicate the direction of movement of substances
• Reabsorption = transfer out of the tubular fluid and returned to peritubular capillaries that surround tubules.
• Reabsorption is a selective process, and the sites of the nephron handle the filtrate in tubules differently.
• Secretion = movement of substances across the tubule epithelium
Renal handling of different substances
Summary-Processes occurring in the Nephron
Filtration
Reabsorption Secretion
Excretion
PROXIMAL CONVOLUTED TUBULE (PCT)
Found in cortex15 mm long and 55µm in diametersingle layer of cellsluminal edges with brush borderconvolution increases length hence
increase contact between tubular cells and luminal fluid thereby facilitating reclamation
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SODIUM AND WATER REABSORPTION
REABSORPTION OF SODIUM
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% NaCl Reabsorbed
♦Proximal Tubule 67% Loop of Henle (Ascending) 25%
Distal Tubule 5%Collecting Duct 2% Excreted in Urine % Variable
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Daily sodium intake = daily sodium loss =10.50g
Sodium gain in the body occurs via:Food intake
Sodium loss in the body can occur via:
menstrual flow in females
feces especially diarrhea
urine
at times GIT loses by vomiting
sweat
hemorrhage where salt and water may be quite high
Daily Sodium Balance
Two pathways of the absorption
Lumen
Plasma
CellsTranscellular
Pathway
Paracellular
transport
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Passive Transport
Diffusion
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NaNa++ HANDLING HANDLING
Reabsorption of 60 - 70% Na+ is by active process. The Na+ reabsorption is associated with Cl- and
HCO3- and H2O.
The reabsorption of Na+ is primary and active and is shown by many arguments.
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The net gain and loss of sodium and water are regulated by the kidney over a wide range
BOTH SODIUM AND WATER ARE:
small
circulate free in plasma
not secreted
reabsorbed above 99% hence their absorption is
linked i.e water reabsorption is dependant on
sodium reabsorption.
COUPLING OF WATER TO SODIUM REABSORPTION IN PCT
COUPLING OF WATER TO SODIUM
REABSORPTION IN PCT
Na+ reabsorption in PCT
Primary Active Transport
Secondary Active Transport
Na+
glucose
Na+
H+
out in out in
co-transport counter-transport (symport) (antiport)
Co-transporters will move one moiety, e.g. glucose, in the same direction as the Na+.
Counter-transporters will move one moiety, e.g. H+, in the opposite direction to the Na+.
Tubular
lumen
Tubular CellInterstitial
Fluid
Tubular
lumen
Tubular CellInterstitial
Fluid
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Transport is abolished by cooling.
Replacement of sodium by any other cation (Lithium) greatly reduces reabsorption of H2O and other solutes.
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Reabsorption continues at almost normal rates after substitution of Cl- by various other anions, nitrate and perchlorate.
Replacement of Na+ with HCO3- reduces
Na+reabsorption, but by less than half
Mannitol in the lumen, reduces [NaCl]
Inhibition of Na+ - K+ ATPase by oubain.
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Na+ EXTRUSION Cl- REABSORPTION
H2O REABSORPTION
UPTAKE OF NaCl AND H2O
The uptake of Na+, Cl- and H2O from lateral intercellular spaces into peritubular capillaries
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Na+
Cl-
Na+
Cl-
H2O πLI
πcap
πLIS
CapillaryLumen
- πcap = capillary hydrostatic pressure - πLIS = oncotic pressure in the lateral spaces + πLIS = oncotic pressure in the capillary + πcap = hydrostatic pressure in lateral
spaces UPTAKE α (πcap + πLIS) – (πLIS + πcap)
H2OπLIS
πcap
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RENAL PHYSIOLOGYRENAL PHYSIOLOGY
LECTURE 3 & 4: CONT’D
TRANSPORT PROCESSES IN THE PROXIMAL TRANSPORT PROCESSES IN THE PROXIMAL TUBULETUBULE
By
DR. P MURAMBIWA
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GLUCOSE AND AMINO ACID REABSORPTION
Glucose & amino acidsCo-transported with sodium
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Transport processes for amino acid transport (Tm limited).
for basic amino acids and cysteine
for glutamic and aspartic acids
for neutral acids
imino acids
for glycine
Glucose / Amino acid Co-Transport-PCT
Na+
Glucose or Amino acid
Na+
H+
out in out in
co-transport counter-transport (symport) (antiport)
Co-transporters will move one moiety, e.g. glucose, in the same direction as the Na+.
Counter-transporters will move one moiety, e.g. H+, in the opposite direction to the Na+.
Tubular
lumen
Tubular CellInterstitial
Fluid
Tubular
lumen
Tubular CellInterstitial
Fluid
CONCEPT OF TRANSPORT MAXIMUM (Tm)
Refers to limit to the amount of substance that the
renal tubule can transport per unit time.
Under normal circumstances Tm is not exceeded but
due to excess ingestion or disease the plasma
concentration of a substance increases and exceed Tm
hence substance appear in urine such as
glycosuria
aminoaciduria
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GLUCOSE TRANSPORT & CONCEPT OF TRANSPORT MAXIMUM
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HYDROGEN ION SECRETION AND HYDROGEN ION SECRETION AND BICARBONATE REABSORPTIONBICARBONATE REABSORPTION
BICARBONATE HANDLING
BICARBONATE IS FREELY FILTRABLE
• it undergoes reabsorption in the • 1)PCT• 2)ASCENDING LOOP OF HENLE
• 3)CORTICAL COLLECTING DUCTS• bicarbonate reabsorption is an ACTIVE
PROCESS VIA:
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• Processes in the kidney that consume most of the hydrogen ions secreted by the tubular epithelium.
• Processes in the kidney that lead to generation of new bicarbonate to replace depleted plasma
bicarbonate reserves.
BICARBONATE REABSORPTION
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BICARBONATE REABSORPTION
bicarbonate reabsorption is an ACTIVE
PROCESS VIA:
HYDROGEN ION ATPase pumps
HYDROGEN ION/POTTASIUM ION ATPase pumps
SODIUM ION/HYDROGEN ION COUNTER-
TRANSPORTERS
BICARBONATE ION EXCRETION = BICARBONATE
FILTERED + BICARBONATE SECRETED-BICARBONATE
REABSORBED
BICARBONATE REABSORPTION STARTS IN THE CELL
carbon dioxide + water = carbonic acid
carbonic acid dissociates to form bicarbonate ion and hydrogen ion
bicarbonate ion is transported to the interstitial fluid then to
plasma while hydrogen ion is actively transported into the
lumen to combine with filtered bicarbonate to form water
and carbon dioxide which diffuse back to the cell for use in
the next cycle of bicarbonate reabsorption
ADDITION OF NEW BICARBONATE TO PLASMA
COMBINATION OF SECRETED
BICARBONATE WITH NON
BICARBONATE BUFFERS
RENAL PRODUCTION AND
SECRETION OF AMMONIUM occurring
in the PCT
RENAL METABOLISM OF GLUTAMINE AND EXCRETION OF AMMONIM ION
• Glutamine (amino acid) can be co transported with sodium or can be from the interstitial fluid where it is metabolized by the cell to form ammonium ion and bicarbonate ion
• the ammonium ion is then secreted in counter transport with sodium to be excreted in urine- this leads to a net gain of bicarbonate ion
Usually about 25 times bicarbonate is filtered
more than any other buffer hence all secreted
hydrogen combine with bicarbonate in lumen
until all has been used up before combining with
other buffers of which hydrogen phosphate is the
most vital
there is a net gain of bicarbonate in this case vital as a
way of compensating acidosis
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ACID PHOSPHATE EXCRETIONACID PHOSPHATE EXCRETION
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REABSORPTION OF UREAREABSORPTION OF UREA
• 50%-reabsorbed by simple
diffusion in the PCT.
• 30% is reabsorbed in the DISTAL
CONVOLUTED TUBULE
• 50% reabsorbed by FACILITATED DIFUSSION
VIA UREA TRANSPORTERS IN THE THIN
ASCENDING LIMBS OF THE LOOP OF HENLE.
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SUMMARYSUMMARY This Lecture identified and described the
following: Pathways for sodium reabsorption across
the proximal tubule epithelium
How Na+ and water reabsorption occur in the proximal convoluted tubule.
How substances like glucose, aminoacids,
Bicarbonate, urea are reabsorbed
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RENAL PHYSIOLOGYRENAL PHYSIOLOGY
LECTURE 5&6: LECTURE 5&6:
COUNTER-CURRENT MULTIPLIER AND EXCHANGE SYSTEMS COUNTER-CURRENT MULTIPLIER AND EXCHANGE SYSTEMS
By
DR. P MURAMBIWA
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CORTEX
MEDULLA
Early diluting segment
Cortical collecting tubule
Outer medullary collecting duct
Inner medullary collecting duct
Thin ascending limb
Thick ascending limb
Thin descending limb
Proximal straight tubule
Proximal convoluted tubule
Bowman’s capsule
Macula densa
Late diluting segment
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INTRODUCTIONINTRODUCTION
The fluid entering the loop of Henle is isotonic toplasma
Animals such as birds and mammals, those with longloops of Henle, urine produced may be moreconcentrated than plasma (hypertonic).
This suggests that some processes that influence movement of water or perhaps some electrolytes.
The loops of Henle are considered to be Counter-currentMultiplier Systems.
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OBJECTIVES:OBJECTIVES:
What is the difference between Counter-current Multiplication and Counter-current Exchange Systems? Describe the role played by: a) loops of Henle, b) vasa recta, c) collecting ducts, d) ADH, and e) urea in the production of an osmotically concentrated urine.
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COUNTER-CURRENT MULTIPLICATION MECHANISMCOUNTER-CURRENT MULTIPLICATION MECHANISM Hypothesis: Proposes that the loop of Henle can produce a small osmotic gradient between the ascending and descending limbs that can be multiplied into a large longitudinal gradient by the countercurrent arrangement in the two limbs.
Wirz, Hargitay & Kuhn (1951)
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Operation of the loop of Henle as a countercurrent multiplier system
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ASCENDING LIMBASCENDING LIMB
Actively extrudes NaCl into the medullary interstitium, but is impermeable to water. Process uses a Na+ - K+ ATPase Cl- is actively transported. Stoichiometry of 1Na+, 2Cl- and lK+
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Much of the K+ leaks back into the tubular lumen so that it is predominantly NaCl that accumulates in the medullary interstitium. Osmolality in the medullary interstitium is increased and that of the fluid in the ascending limb is decreased.
NaCl transport in the thick ascending limb of the loop of Henle
Na+ reabsorption in thick ascending loop of Henle
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THE DESCENDING LIMBTHE DESCENDING LIMBHighly permeable to H2O and to a lesser extent to NaCl Urea is added to the medullary interstitium from the collecting duct by diffusion down a concentrationgradient Collecting duct tubules urea concentration rises because of water reabsorption. The medullary collecting tubule is permeable to urea in the presence of antidiuretic hormone (ADH).
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THE OSMOTIC GRADIENTTHE OSMOTIC GRADIENT
• Only juxtamedullary nephrons contribute
• NaCl is added to the medullary interstitium.
• Ascending limb is highly impermeable to H2O.
• H2O extraction from the descending limb
increases the [NaCl]
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• In the cortical collecting duct system, in the presence of ADH, the osmolality increases to become iso-osmotic with plasma.
• High [urea] in the medullary interstitium provides an osmolality additional to that of NaCl.
Na+ Reabsorption-Cortical Collecting Duct
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UREA AND COUNTER-CURRENTUREA AND COUNTER-CURRENT MULTIPLICATIONMULTIPLICATION ♦Urea is delivered to the distal tubule and hence the collecting ducts. ♦ In the presence of ADH water is reabsorbed. ♦ In the medullary collecting ducts ADH causes the urea and water reabsorption. ♦The high interstitial urea concentration leads to the diffusion of some urea into the loop of Henle, to return to the collecting duct.
ADH/Arginine vasopressin
UREA DISTRIBUTION 50%-reabsorbed by simple diffusion in the PCT.
30% is reabsorbed in the DISTAL CONVOLUTED TUBULE
50% reabsorbed by FACILITATED DIFUSSION VIA UREA TRANSPORTERS IN THE THIN ASCENDING LIMBS OF THE LOOP OF HENLE.
15% LOST IN URINE DAILY.
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SUMMARY OF THE FEATURES THAT PROMOTE COUNTERCURRENT MULTIPLIER
COUNTERCURRENT MULTIPLIER -basically depends on the ability of the loops of henle to create and maintain a hyper-osmotioc medullary interstitium.
Features making this possible are:apposition of the thin descending and thin ascending loops of Henle (hairpin turn of the loops of henle)
apposition of the vasa recti (vessels originating from the efferent arteriole-hairpin turn of the vasa recti)
the thin descending limb is impermeable to sodium chloride but permeable to water
the thin ascending limb is impermeable to both sodium chloride and water and has no active transport mechanism for sodium chloride
The thick ascending limb is impermeable to both water and sodium chloride but has active transport for sodium chloride
the distal tubule has active transport for sodium chloride but is impermeable to water
the cortical collecting duct is permeable to water, & has active transport for sodium chloride
Both medullarly and cortical collecting ducts are controlled by vasopressin.
urea, a freely permeable and highly filtrable substance also helps in the maintenance of a hyper osmotic intestitium in the medulla.
Countercurrent exchanger system- Vasa recta
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COUNTERCURRENT EXCHANGE SYSTEMCOUNTERCURRENT EXCHANGE SYSTEM
Vasa recta = capillaries from efferent arterioles of the juxtamedullary nephrons
Blood flow = 50 - 100 ml/min of which perhaps 5 ml/min reaches the papillae.
The vasa recta have a hairpin arrangement and dip down into the medulla.
This arrangement ensures close contact between ascending and descending vasa recta and between ascending and descending loops of Henle.
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The vasa recta, like capillaries, elsewhere are permeable to water and solutes.
In the ascending vasa recta the plasma regains the water and solutes.
O2 and CO2 also undergo a countercurrent exchange in
the vasa recta. As the descending vasa recta enter the increasingly
hypertonic medullary interstitium, water is osmotically abstracted from the blood vessel, so that the osmolality of the blood (and its viscosity) are increased.
IN SUMMARY THE COUNTERCURRENT
EXCHANGER-OCCURS IN THE VASA RECTI BY
SIMPLE DIFFUSION OF SODIUM CHLORIDE
INTO, AND WATER OUT OF THE DISCENDING
LIMB WHILE IN THE ASCENDING LIMB THERE IS
DIFFUSION OF SALT OUT, AND WATER INTO THE
LIMB HENCE MEDULLARLY SALT WASHOUT IS
PREVENTED.
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LECTURE SUMMARY
The Counter-current mechanism permits the kidney to excrete urine with varying osmolalities. The primary event in this process is active NaCl transport out the thick ascending limb of the loop of Henle into the medullary interstitium.
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ACTIVITY 4ACTIVITY 4
1. How do processes for sodium and water reabsorption in the collecting ducts and proximal convoluted tubules differ?
2. Describe the role of counter-current
multiplier system in urine concentration.
3. State how changes in medullary blood flow or loop flow rates may impede concentration of
urine.
4. State the action of ADH and the nephron sites on which it acts.
RENAL PHYSIOLOGYRENAL PHYSIOLOGY
LECTURE 7 & 8:
THE RENAL CONTROL OF SODIUM AND POTASSIUM EXCRETION
&RENAL ACID BASE BALANCE
By
DR. P MURAMBIWA
OBJECTIVESOBJECTIVES:
1a. Explain renal sodium and potassium handling and factors that control their handling.
1b. What determines the effectiveness of a pH buffer?
2. List chemical buffers present in:
(a) extracellular fluid (b) intracellular fluid (c) bone (d) urine
3. What leads to the generation of new bicarbonate in the kidney to replace depleted plasma bicarbonate reserves?
4. Which process in the kidney consumes most of the hydrogen ions secreted by the tubular epithelium?
THE RENAL CONTROL OF SODIUM AND POTASSIUM EXCRETION
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• In several types of disease, Na+ balance becomes deranged by the failure of the kidneys to excrete Na+ normally.
• The processes involved in renal Na+ handling are discussed in this Lecture to enable you to understand underlying factors that may be associated with impairment in kidney function.
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• Conditions associated with NaConditions associated with Na++ Deficiency. Deficiency. ♠ Disorder Manifestation
• Severe diarrhoea hyponatremia especially
infants • Diuresis hyponatremia• Severe sweating hyponatremia• Adrenal insufficiency hyponatremia • SIADH ( Inappropriate hyponatremia
ADH secretion).
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• Diseases associated with KDiseases associated with K++ deficiency. deficiency.♥ Disorder Manifestation.
• Laxatives hypokalaemia • Vomiting hypokalaemia• Diarrhoea hypokalaemia• Gastrointestinal hypokalaemia• Surgical drainage loss hypokalaemia• Metabolic alkalosis hypokalaemia• Metabolic acidosis hyperkalaemia
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TUBULAR NaTUBULAR Na++ REABSORPTION REABSORPTION
• Controlled by both humoral factors and physical factors.
• Sites = proximal tubule, ascending loop of Henle, distal tubule and the collecting duct or a combination of these sites.
An alteration in GFR changes the filtered
Na+ load
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Na+ EXCRETION
• GFR can be altered is by changing
glomerular capillary pressure.
• Hydrostatic and plasma oncotic pressures can also influence tubular handling of Na+.
• Hydrostatic and plasma oncotic pressures in the peritubular.
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• Increases in blood pressure (30-60mmHg) above control values (105 - 130 mm Hg) in
anaesthetised rats have been seen to cause natriuresis.
Suggested that arterial blood pressure wash
out an osmotic gradient to decrease not only in Na+ reabsorption, but also in the ability of
vasopressin to concentrate urine.
♣ Renal vasodilation in anaesthetised dogsinduced by either Ach or prostaglandin has
been noted to increase Na+ excretion and urine flow without changes in GFR.
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PHYSICAL FACTORSPHYSICAL FACTORS
• Changes in the blood perfusing the kidneys
• Expansion of the ECF volume leads
to increased blood volume and
increased systemic arterial pressure.
• Increased fluid pressure decreases proximal tubular Na+ reabsorption.
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• Increased blood volume also causes a dilution of plasma proteins by that lowering plasma oncotic (colloid osmotic) pressure.
Physical factors, HOWEVER, play only a subsidiary role in regulating sodium excretion.
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NEURAL CONTROLNEURAL CONTROL
☻Claude Bernad (1859) showed that section of the greater splanchnic nerve (interruption of a major part of the sympathetic supply to the kidney) increased urine flow in the anaesthetised dog.
• Interruption of a major part of the sympathetic supply to the kidney increases urine flow.
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♥ Sympathetic fibres from the splanchnic nerves enter the kidney as a nerve plexus along the walls of the renal artery.
• Sympathetic fibres from the splanchnic nerves innervate three distinct structures
♥ the renal vasculature, particularly along the arteries and arterioles;
♥ the juxtaglomerular apparatus;
♥ the proximal tubule and other parts of
the nephron.
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– The nerve-mediated Na+ reabsorption involves an initial activation of ∝ 1
adrenoceptors.
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♦ HORMONAL REGULATION
Condition Na+
mmol/l K+
mmol/l Cl- mmol/l
HCO3-
mmol/l
Normal
Adrenal insufficiency (Addison’s disease)
Primary Aldosteronism
142
120
148
4.5
6.7
2.4
105 85
96
25
25
41
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• Aldosterone is involved in the regulation of Na+ reabsorption.
• Site of action is the epithelial cells of the distal convoluted tubules and collecting ducts.
• Glandular epithelial cells in the bowel mucosa, salivary and sweat glands.
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• Aldosterone is implicated in instances of fluid and electrolyte abnormalities associated with some diseases.
• Increased quantities of ALDOSTERONE in the urine of patients
with primary and secondary hypertension, congestive heart failure, liver cirrhossis and nephrosis
• Elevated levels of aldosterone are also found in the urine of pregnant women.
• Aldosterone promotes Na+ reabsorption in exchange for increased excretion of K+, H+ and NH4
+ ion in humans.
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Nuclear membraneCell membrane
(Transcription)
(TRANSLATION) mRNA ribosomesavidin
DNAAcidic protein
♦ MECHANISM OF ALDOSTERONE ACTIONMECHANISM OF ALDOSTERONE ACTION
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• Mineralocorticoid Escape Phenomenon
∀ ♦♦ EFFECTS ON GFR AND RBFEFFECTS ON GFR AND RBF
• Aldosterone and glucocorticoids are necessary for the maintenance of GFR and RBF.
♦♦ ALDOSTERONE SYNTHESISALDOSTERONE SYNTHESIS
• ACTH promotes steroidgenesis in the adrenal cortex
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• Angiotensin II and plasma levels of Na+ or K+
• Plasma sodium (PNa+ )
• K+ ions also exert a stimulatory effect on aldosterone biosynthesis by acting directly on the zona glomerulosa cells
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♦♦RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)(RAAS)
Influences Na+ excretion in two different ways.
A direct renal action of AII
An influence of AII over aldosterone synthesis
AII acts directly on the adrenal cortex to enhance
aldosterone synthesis.
Macula densa cells within the distal tubule are
believed to act as sensors.
Maculadensa(vasoconstrictorsand vasodilators)
Efferentarteriole
Glomerularcapillaries
Proximaltubule
Bowman’s capsule
Urinary space
Juxtaglomerular(Granular) cells(renin)
Renalnerves
Afferent arteriole
Distaltubule
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• Alteration of NaCl concentration is accompanied by changes in renin secretion.
(plasma globulin synthesized by the liver) Angiotensinogen
↓ Renin (Aspartyl proteinase)
Angiotensin I (Decapeptide)↓ Converting Enzyme in Pulmonary
Circulation INHIBITED BY CAPTOPRIL
Angiotensin II (Octapeptide) ↓ INHIBITED BY SARALISIN Angiotensin III
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♦♦ RENIN RELEASERENIN RELEASE
• Increased sympathetic activity
Reduction of the extracellular fluid volume and/or the effective circulating volume will decrease systemic arterial blood pressure.
• Baroreceptor reflexes will subsequently increase sympathetic activity to arterioles.
• The main baroreceptors are in the carotid arteries (carotid sinuses).
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Sympathetic nerve activity causes renin release, mediated by α 1-adrenergic receptors and activated
by circulating catecholamines
Decreased wall tension in the afferent arterioles.
• Decreased renal perfusion pressure leads to increased renin release from the granular cells.
• The macula densa mechanism
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• Changes in the delivery of NaCl to the macula densa (composition of fluid in ascending limb detected)
• The macula densa stimulus releases PGI2 that
acts on the granular cells to release renin.
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♦♦ EFFECTS RAASEFFECTS RAAS A II constricts efferent arterioles, to reduce peritubular capillary pressure.
A II increases reabsorption of Na+ in the distal tubule.
A II promotes aldosterone synthesis in
the zona glomerulosa. Stimulates thirst sensation in the brain.
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2934
Tubuloglomerular feedback
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• De Bold (1982) demonstrated that the artrial extracts caused a rapid 30-fold increase in NaCl excretion coupled with an increase in urine flow in the rat.
• Atrial cardiac cells produce ANP. • Atrial stretch leads to an increase in the circulating level of ANP.
• Effects of ANP are modulated via specific cell surface receptors that when bound to,increase intracellular levels of cyclic guanosine monophosphate (cGMP).
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• Atrial extracts increase GFR in isolated perfused kidney.
• A high density of ANF receptors has been seen in adrenal glomerulosa membranes.
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♥♥ ACTIONS OF ANPACTIONS OF ANP
♠Inhibition of aldosterone secretion
♠Reduction of renin release
♠Reduces the release of vasopressin
♠Natriuresis and diuresis.
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▲ ▲ ANP/ALDOSTERONEANP/ALDOSTERONE
• A high density of ANF receptors has been seen in adrenal glomerulosa membranes.
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REGULATION OF BODY KREGULATION OF BODY K++
• Body K+
= contains 3 - 4 mmoles = 2% of this is extracellular and its maintenance
is essential for life. = Maintenance = regulation of renal excretion.
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• RENAL HANDLING OF KRENAL HANDLING OF K++
♦In the proximal tubule 80-90% of the filtered K+ is reabsorbed. ♦In the descending (thin) limb of the loop of
Henle, K+ is secreted, but K+ is reabsorbed from the ascending limb with Na+ and Cl-. ♦In the early distal tubule that is functionally similar to the ascending limb of Henle, Na+, Cl- and K+ reabsorption occurs.
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♦The late distal tubule and subsequent segments of the collecting duct system
secrete K+ into the tubular fluid. ♦The rate of K+ secretion is also influenced
by the rate of Na+ reabsorption.
♦Diuretics will increase the rate of K+ secretion.
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KK++ EXCRETION EXCRETION
• Aldosterone is the only hormonal control
over K+ output.
• The K+ losing effects of aldosterone do not exhibit the "escape phenomenon.
• Increases in plasma concentration of K+
directly influence aldosterone synthesis.
Summary of Na+ and K+ handling
Strenuous exercise
Cell lysis
Metabolic acidosisMetabolic Alkalosis
B-adrenergic blockadeB-adrenergic stimulation
Aldosterone deficiency (addison’s disease)
Conn’s syndrome (excess aldosterone)
Insulin deficiency (diabetes mellitus)
Insulin
Factors that shift K+ out of cells (Increase EC K+)
Factors that shift K+ into cells (Decrease EC K+)
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• HYPOKALAEMIA CAUSESHYPOKALAEMIA CAUSES • Gastrointestinal tract or kidneys losses Persistent vomiting or diarrhoea or the use of diuretics
• Excess insulin.
• Insulin increases K+ entry into cells that the extracellular levels fall.
• Alkalosis reduces proximal tubular HCO-
3 absorption and reduces Na+ reabsorption, therefore more NaHCO3 and water in the tubule.
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• EFFECTS OF HYPOKALAEMIAEFFECTS OF HYPOKALAEMIA
Symptom free until plasma K+ level has fallen to approximately 2 - 2.5 mmol/l.
• Initial symptom is muscle weakness until death occurs when the respiratory function is affected.
In hypokalaemia the time cardiac muscle takes to
repolarize = prolonged.
K+ deficiency also causes derangements of metabolism.
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Hypokalaemia also affects vascular tone, causing vasoconstriction. Polyuria and thirst are present because the renal response to ADH is impaired by hypokalaemia that patients are unable to produce urine. Treatment consists of oral administration of potassium salt.
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HYPERKALAEMIA CAUSESHYPERKALAEMIA CAUSES
• Ingestion of excess K+ causes a rise in plasma levels of K+.
• Acidosis may also cause hyperkalaemia when the body's K+ stores are normal.
• Insulin causes entry of K+ into cells, therefore deficiency will lead to hyperkalaemia.
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• Another cause of hyperkalaemia is breakdown of cells as in severe trauma, or
treatment with cytotoxic drugs.
• Hyperkalaemia can also occur due to decreased K+ excretion in renal failure due reduction in functioning nephrons.
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EFFECTS OF HYPERKALAEMIAEFFECTS OF HYPERKALAEMIAExcitable cells are unable to conduct action
potentials and muscle weakness follows. Loop diuretics can be used to promote K+
excretion. Insulin can also be used to promote K+ entry into
cells. The effects of hyperkalaemia on muscle can be
corrected by Ca2+ administration.
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♦♦ RENAL CALCIUM HANDLINGRENAL CALCIUM HANDLING
• In the proximal tubule, calcium reabsorption parallels
that of sodium and water.
• Ca2+ is positively charged and therefore entry into the tubular cell is favoured by the electrical gradient.
• A calcium-activated ATPase facilitates transport.
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• In addition a Ca2+ counter transport out of the cell coupled to passive Na+ entry occurs (ratio 3Na+ entering for 1Ca++ leaving).
• Ca2+ reasorption in the ascending limb of the loop of
Henle is similar to that has been described before for the proximal tubule.
• Furosemide that inhibits NaCl transport in this region also inhibits Ca2+ reabsorption.
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A Ca2+- ATPase facilitates Ca2+ transport in the ascending limb of the loop of Henle.
Calcium is reabsorbed under the influence of parathormone.
The physiological regulation of Ca2+ reabsorption occurs in the cortical thick ascending limb and distal tubule.
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♦♦ HANDLING OF PHOSPHATEHANDLING OF PHOSPHATE
Two forms acid phosphate,
• Acid H2PO4- and alkaline phosphate HPO=
4.
Phosphate is freely filtered in the nephron.
Ratio of 4:1 alkaline to acid phosphate is present in
the filtrate.
• The only hormone that regulates renal tubular phosphate transport is PTH.
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• Other hormones such as calcitonin, glucagon and insulin may also influence renal phosphate transport.
• PTH, calcitonin and glucagon increase renal
phosphate excretion while insulin reduces phosphate excretion.
• Hypocalcaemia is common in renal failure patients.
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• Acidosis decreases the plasma levels of ionized Ca++ while alkalosis has the opposite effect.
• The characteristic feature of low plasma
calcium is tetany, convulsions and muscle cramps.
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SUMMARY-CONTRIBUTION OF THE SUMMARY-CONTRIBUTION OF THE DIFFERENT NEPHRON SEGMENTSDIFFERENT NEPHRON SEGMENTS
• Nephron segment Major Functions
____________________________________
Glomerulus Forms an ultrafiltrate of plasma
Proximal tubule Reabsorbs isosmotically 70 percent of the filtered NaCl and H2O
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• Proximal tubule Reabsorbs K+, glucose amino acids, calcium, phosphate, magnesium, urea, uric acid, and bicarbonate (by H+secretion)
Secretes H+, ammonia, and organic acids and bases
• Loop of Henle Countercurrent multiplier; reabsorbs NaCl in excess of H2O.
Major site of active regulation of magnesium excretion
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• Distal tubule Reabsorb a small and connecting fraction of filtered segment NaCl Major site of
active regulation of
calcium excretion
• Collecting tubules Site of final modification of the urine;
Reabsorb NaCl; urine NaCl concentration can be reduced to less than 1 mmol/L
RENAL ACID BASE BALANCE
WHY MAINTAIN ACID WHY MAINTAIN ACID BASE BALANCE?BASE BALANCE?
Requirements for normal metabolism
• Fluctuations in pH cause significant changes in H+ concentrations.
• The pH of the blood of a normal man is alkaline and it is maintained within a small range of about 7.37 to 7.42.
BICARBONATE BUFFER SYSTEMBICARBONATE BUFFER SYSTEM
[H+] nmol/l
pH pCO2
(mm-Hg)[HCO-
3]
m mol/l
Arterial 40 7.42 40 24
Venous 46 7.35 46 25
MAJOR SOURCES OF ACIDMAJOR SOURCES OF ACID CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO-
3
In Western diets approximately 40 to 60 mmoles of non-carbonic acids mainly from protein metabolism. Phosphoric acid from the catabolism of phospholipids makes a minor contribution to daily production of non- carbonic acids.
OTHERSOTHERS
The production of lactic acid during muscular exercise and during hypoxia The production of aceto-acetic acid and β - OH butyric acid during uncontrolled diabetes mellitus Therefore it is vital that a mechanism be developed to defend the system from fluctuations in H+ ions.
BUFFERS OF THE KIDNEY
HCO-3/CO2
Phosphate
Ammonia
HCO-3/CO2
Phosphate
Ammonia
CO-3/CO2
HCO-3 regulated in proximal tubule – distal
tubule and collecting duct
PhosphateTwo phosphate salts disodium hydrogen phosphate (alkaline) Na2HPO4
Sodium dihydrogen phosphate (acid) NaH2PO4 .
The normal ratio 4 :1 alkaline to acid and can be changed H+ secretion - mainly distal tubule
AmmoniaConversion of glutamine to glutamic acid and α- ketoglutarate NH3 diffuses into the tubule to combine with H+
forming NH4+ that has a much lower permeance
than NH3.
The kidney can greatly increase NH3 production
in acidosis.
This is one of the main ways in which the kidney responds to an acid load.
EFFECTS OF DISTURBANCES OF pHEFFECTS OF DISTURBANCES OF pH
♣ Hyperkalaemia due to movement of potassium from cells into the extracellular fluid and the depression of renal secretion of K+
♥ Widespread loss of smooth muscle tone that
produces a severe drop in arterial pressure. For prolonged periods (weeks to months) leaching of minerals from bones (osteoporosis).
Effect of decreased H+ ion concentration raised
pH is tetany or spasm of muscles.
ACID BASE DISTURBANCESACID BASE DISTURBANCES
Divided into two categories
♣ Disturbances of Respiratory origin Respiratory acidosis
Respiratory alkalosis
♣ Disturbances of Non-Respiratory origin Metabolic acidosis Metabolic alkalosis
♦ "Metabolic" refers to acid-base disturbances
that effect the CO-3/CO2 buffer system by
means other than altering pCO2.
RESPIRATORY ACIDOSIS♣ The respiratory system is unable to remove sufficient pCO2 from the body to maintain normal pCO2.
[CO2] + H2O ⇔ H2CO3 ⇔ HCO-
3 + H+
♣ Consequence = ↑↑ [H] and ↑ [HCO-3] pH
RENAL COMPENSATIONRENAL COMPENSATION
♦ Definitions•Compensation is the restoration of
pH towards normal though [HCO-3]
and/or pCO2 is still disturbed.
•Correction is the restoration of normal pH, [HCO-
3] and pCO2.
♣ A change in [H+] = H+ secretion from the renal tubular cells. ♣ Sufficient to reabsorb HCO-
3 though plasma HCO-3
is raised – therefore generates increased HCO-3 for
the plasma. ♣ The increased H+ leading to increased plasma[HCO-
3] is the RENALCOMPENSATION for respiratory
acidosis. ♣ The pH is restored to normal but [HCO-
3] is elevated.
♣ Respiratory acidosis is associated with hypercapnia, pCO2 = 48 mmHg in arterial blood.
♥ CAUSES OF RESPIRATORY ACIDOSISCAUSES OF RESPIRATORY ACIDOSIS
Chronic bronchitis
Obstruction of airway by a foreign body
Mechanical injuries of the chest
Infections directly affecting the respiratory centre and brain stem.
Anaesthetics such as morphine barbiturates, depressants of respiration
RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS♣ Excessive removal of CO2 from the
body = arterial pCO2 below 35mmHg.
↓CO2 + H2O ⇔ H2CO3 ⇔ ↓ ↓ H+ +
↓HCO3-
↓
pCO2 and consequent in [H+] in the renal
tubule H+ secretion ♣ Therefore, HCO-
3 is excreted in the urine and
plasma [HCO-3] falls further.
♣ In the kidney the defect leads to a change in pH increasing H+ ions in the blood that will lead to
decreased H+ secretion and therefore HCO3-
reabsorption.
METABOLIC ALKALOSISMETABOLIC ALKALOSIS♣ Acid base disturbances by means other
than altering the pCO2
= pH = H+ in the blood = H+
secretion = HCO3- re-absorption.
H2O + CO2 ⇔ H2CO3 ⇔ H+ + ↑↑ HCO3
-
+ OH-
♣ Metabolic alkalosis = addition of OH-
ions
♣Hypoxia = respiration = hypocapnia- hyperventilation = respiratory alkalosis.
♣The decreased level of H+ acts on the chemo-receptors to reduce ventilation resulting in the increase of pCO2.
♣This is RESPIRATORY COMPENSATION
for metabolic alkalosis.
♣ This compensation brings down the pH, but further increases the plasma concentration of HCO3
-.
♣ The reduced H+ secretion in the renal tubules leading to low HCO3
- is the RENAL
COMPENSATION for renal alkalosis
METABOLIC ACIDOSISMETABOLIC ACIDOSIS♣ Caused by excessive ingestion of acids
and production of H+ ions from the body.
♣ Addition of H+ ions drives the reaction to the left resulting in the depletion of
plasma levels of HCO3-.
CO2 + H2O ⇔ H2CO3 ⇔ H+ + ↓↓ HCO3-
+ H +
♣ This direct loss of HCO3- leads to a
change in pH.
– This change in pH acting on the chemoreceptors stimulates respiration so that pCO2 falls. This is respiratory
compensation for metabolic acidosis.
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SUMMARYSUMMARY • The kidneys are the major site of sodium output and
regulation of extracellular fluid volume. • Renal Na+ excretion is influenced by GFR, aldosterone,
peritubular capillary
• Starling forces, renal sympathetic nerve activity, diuretics etc. • The kidneys normally maintain potassium balance by
excreting most ingestedpotassium.
SUMMARY CONTINUED The kidney is involved in the maintenance of pH.
• The processes involved include regulation of H+ secretion.
• Urinary acidification involves re-absorption of filtered bicarbonate, excretion of acid and ammonia.
• The kidneys compensate for acidosis by
adding large quantities of new bicarbonate to the blood.
• When an individual is acidotic for more than a few
days, there occurs a marked increase in ammonia synthesis.
• When an alkalosis exists, the kidneys compensate by secreting too little acid to accomplish complete re-absorption of filtered bicarbonate, thus leading to excretion of bicarbonate
• A diuretic is a substance that increase the rate of urine output.
• It cause natriuresis (increased sodium output), and this in turn cause diuresis (increased water output)
Diuretics and their mechanisms
Early distal tubuleInhibit H secretion and HCO-3 reabsorption
Thiazides (chlorothiazides)
Thick ascending limb
Inhibits Na-K-Cl co-transport in
luminal membrane
Loop (Furosemide)
Mainly proximal tubule
Inhibit water and solute reabsorption
Osmotic (Mannitol)
Site of actionMechanism of action
Class of diuretics
Collecting tubulesBlock entry of Na into the channels
of luminal membrane
Sodium channels blockers
(Amiloride)
Collecting tubulesInhibit aldosterone action
Competitive inhibitors of aldosterone
(Spironolactone)
Proximal tubuleInhibit secretion of H+ and
reabsorption of HCO-3
Carbonic anhydrase Inhibitors
(Acetazolamide)
• Basic processes involved in the filling and emptying of the bladder
3 muscles are involvedDetrusor muscle-smooth
(parasympathetic)Internal urethral sphincter-smooth
(sympathetic)External urethral sphincter-skeletal
(somatic motor neurone)
MICTURITION OR URINATION
Micturition reflex
stretchreceptors
• 1) APs generated by stretch receptors
• 2) reflex arc generates APs that
• 3) stimulate smooth muscle lining bladder
• 4) relax internal urethral sphincter (IUS)
• 5) stretch receptors also send APs to Pons
• 6) if it is o.k. to urinate
– APs from Pons excite smooth muscle of bladder and relax IUS
– relax external urethral sphincter
• 7) if not o.k. inhibitory impulses from pons inhibit micturition
–
Micturition reflex
THE END