Download - Kidneys Online
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Kidneys
Sherif Elsobky
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Aims
To explore the bare essentials of nephrology
Help to tackle big bulky renal questions
Can not cover all content Will highlight what you need to learn
You will need to read over and consolidate
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Topic to cover
Anatomy
The nephron
Hormones
Acid base
Clinical
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Kidney Introduction
10-12 cm in length
Retroperitoneal
T5 and L3
Left is higher
Outer cortex and inner medulla
Functional unit is a nephron
Blood filtered at about 150 litres/day
25% of CO
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Renal functions
Impressive organ for its size!
ABCDEF
Acid-base
Blood pressure
Ca
D vitamin
EPO
Filtration
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External Anatomy
External kidney
Renal fascia: Most outerlayer of connective tissue,
connects kidneys toabdomen
Adipose capsule:Cushing's the kidneys
Renal capsule: Smoothconnective tissue
Blood supply
Renal artery AA
Renal vein IVC
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Internal Anatomy
Inner Kidney
1) Ureters
2) Renal pelvis
3) Renal cortex4) Renal medulla
5) Renal pyramid
6) Renal column
7) Renal papilla8) Minor calyx
9) External capsule
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Which structures from previous slide would be visible
on an intravenous urogram/pyelogram?
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Blood supply
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Aims
Anatomy
The nephronHormones
Acid baseClinical
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The nephron
Functional unit of a kidney
Approx 1 million/kidney
There are two types of nephrons short cortical
nephrons and large juxtamedullary nephrons
that extend down into the medullary pyramids
Aim of a nephron is to concentrate urine and
reabsorb solutes.
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The Nephron
Bowmans capsule
Glomerulus
Proximal
convoluted tubule
Capillary
Loop of Henl
Collecting duct
Distil convoluted
tubule
Branch of renalartery
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Question!
Which parts of the nephron are in the cortex
and which parts are in the renal medulla
Answer:
Medulla: Loop of Henle, collecting duct
Cortex: Bowmans capsule, PCT, DCT
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Physiology
Three main functions of a nephron to produce urine:
Glomerular filtration
Tubular reabsorption
Tubular secretion
Four main methods of reabsorption/secretion in tubules:
Osmosis e.g. H20
Active transport e.g. Na+/K+ pumps
Electrical gradient e.g. Na+/Cl- pumps Endocytosis e.g. peptide hormones in proximal tubule
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Which part of the nephron is impermeable to
water?
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Variable permeability to
water
Impermeable
to water
Freely permeable
to water
The nephron osmoregulation
Morea
ndmoresalty
H2O
H2O
H2O
H2O
H2O
H2O
Collectingduct
Loop of
Henl
H2O
H2O
Na+
Na+Na+
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Bowmans capsule
Cup-like sac
Performs the first step in the filtration of blood to form urine
Has a glomerulus (hand in fist)
Capillaries of Bowmans capsules are supplied by an afferentarteriole and drained by an efferent arteriole
Two cellular layers separate the blood from the glomerular filtratein Bowmans capsule: The capillary endothelium and the specializedepithelium of the capsule
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Properties
Glomerular capillaries are 50x more permeablethan skeletal muscles
Capillary walls are one cell thick
They are pierced with fenestrations
Proteins do not pass (due to basal lamina layerand negatively charged properties due tosialoproteins (repels albumin)
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Bowman's capsule
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Questions commonly asked about
Bowmans capsule
Label Bowmans capsule
What are the properties of Bowman's capsule
Explain the mechanism of ultrafiltration
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Bowman's Capsule
Functional anatomy
Fenestrations ofglomerular endothelialcells allows for a greaterfunction of filtrationfraction
Basal lamina andpedicles preventsfiltration of largerproteins
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Podocytes
Function of podocytes?
Mechanical support to
filtration membrane
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Mesangial cells
Contractile cells that play a role in the
regulation of glomerular filtration
Mesangial cells secrete extracellular matrix,
take up immune complexes and are involved
in the progression of glomerular disease
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Glomerular filtration
Blood enters the glomerulus from RA
Resistance of efferent arterioles greater than theafferent arterioles
This produces a high pressure gradient that leadsto ultrafiltration of plasma through the bowman'scapsule
Osmotic pressure of plasma proteins (oncoticpressure) opposes filitration
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GFR
Rate of filtered fluid through the kidney
Usu around 125ml/min
A decreased GFR may be a sign of renal failure
CCR: volume of blood plasma that is cleared ofcreatinine per unit time
useful measure for approximating the GFR
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What factors influence GFR ?
Answers:
Blood pressure
Renal blood flow
Obstruction to urine outflow
Loss of protein-free fluid
Hormones: Renin, Aldosterone,
ADH, ANP
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PCT
Made up of a singlelayer of cells that areunited by apical tight
junctions
Luminal edges of thecells have striate brushborder due to thepresence of manymicrovilli
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PCT 2
70% of water is reabsorbed
All of the glucose and amino acids
Regulates blood pH and salt
Urea is left behind and even secreted into thetubules
Reabsorbed molecules pass into thesurrounding capillaries
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Loop of Henle anatomy
Have thin and thick portions of the limb
Thick portions contain mitochondria to
facilitate active transfer of electrolytes
Ascending limb is impermeable to water
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Thou sodium goes, water shall follow
Sherif Elsobky
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Loop of henle physiology
1. The descending limb is impermeable to ions but premable to H20
2. The ascending limb is impermeable to H20 but not to ions
3. Na-K-2Cl co-transporter actively transports solutes from the thick ascending limb (orpassively in thin section) into interstium
1. This is the co-transporter furosemide acts on
4. Water moves through the descending limb via osmosis
5. Urea which was absorbed into the medullary interstium from the collecting duct, diffusesinto the ascending limb (this helps to concentrate urine) and lowers water potential
6. Interstitial fluid diffused into the vasarecta which prevents an equilibrium from forming
The aim of the loop of Henle is to create a hypertonic environment in the renal medulla to allowre-absorption of water from the collecting duct thus concentrating the urine.
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Vasa recta
These vessels branch off the
efferent arterioles of
junxtamedullar nephrons(those nephrons are closest to
the medulla), enter the
medulla and surround the loop
of Henle efferent arterioles of
juxtamedullary nephrons
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Counter-current mechanism
1. The fluid in the tubule become hypotonic as it movesdown the descending limb
2. Hypertonic in ascending limb
3. Vasa recta absorbs interstitum fluid(to preventequilibrium formation)
4. This produces a countercurrent mechanism whichallows the formation of concentrated urine
5. The longer the loop of Henle the more concentratedthe urine
AIM IS TO PRODUCE HYPERTONIC URINE!
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DCT and collecting ducts
DCT: Na-CL transporter, CL leaks throughchannels
Parathyroid hormone increases Ca++
reabsorption Collecting ducts:
Principle cells (Na+/K+-ATPase pumps)
Aldosterone regulated
Intercalated cells (H+-ATPase and H+/K+ exchanger)
Aquaporin channels
ADH regulated
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RAAS
Renin converts the plasma protein
angiotensinogen to angiotensin I
Angiotensin converting enzyme (ACE) in the
lungs, converts angiotensin I to angiotensin II
ANG II +: Sympathetic response
Aldosterone release
Vasoconstriction
ADH
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RAAS
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Antidiuretic Hormone
Baroreceptors/osmoreceptors stimulate the posterior pituitary to
release ADH
Stimulates V2 (G-protein coupled receptor)
Results in an increase in the number of aquaporin -2 receptors over
the collecting ducts
3 billion molecules of water a second move through each aquaporin
ADH also stimulates peripheral vasoconstriction V1 receptors
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ADH mode of action
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Aldosterone
Stimulated by ACE II, ACTH, K+
Released from zona glomerulosa layer (mostouter layer) of adrenal glands
+ mineralocorticoid receptor within theprincipal cells of the DT & CD to up regulateNa+/K+ receptors
Clinical: Spironalactone
Conns syndrome
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EPO
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Vitamin D Cycle
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Aims
Anatomy
The nephron
Hormones
Acid baseClinical
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Acid-Base balance
pH is regulated by the kidney and lungs
Kidney: excretion of acid anions and
reabsorption of bicarbonate
Renal system is the only way H+ can be
excreted from the body
Two different locations:
PCT (mainly)
DT
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What you need to know??
PCT cells contain Carbonicanhydrase which converts CO2+H20 H2CO3
H2CO3 basically becomes
divorced (H+ and HCO3) and goesinto separate directions
H+ goes through the apicalmembrane though Na-Hexchange
The H+ can not be left free as pH
will become very acidic Therefore it reacts with three
main buffers: HPO4, NH3, CO2 & H20 (CA)
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Ammonium (NH4) is produced predominantlywithin the proximal tubular cells.
The major source is from glutamine
Ammonium is produced from glutamine by theaction of the enzyme glutaminase.
Ammonium is a buffer
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Aims
Anatomy
The nephron
Hormones
Acid base
Clinical
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Renal failure
Acute vs Chronic
Pre-renal, renal and post-renal failure
Investigations
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5 stages of CKD
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Acute vs Chronic
Can sometimes be difficult to differentiate
In chronic patients tend to have:
Less symptoms
Smaller kidneys
Anaemia
Low Ca2+ Hypertension
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Diuretics
Mechanisms
Which area of the nephron they act
Side effects
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Examples of diuretics
Carbonic anhydrase inhibitors: Acetazolamide
Loop diuretics: furosemide, torasemide
Thiazide diuretics: bendroflumethiazide
Potassium-sparing: Spironalactone/eplerenone
Osmotic diuetics: Mannitol
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Common investigations
Bloods: FBC (anaemia), U&Es, Ca++
GFR.
Urinalysis: is a simple means of assessing for renaldisease.
ABGs: helps identify acid-base concerns.
Imaging: Ranges from ultrasound to arteriography and
can uncover many pathologic events Kidney biopsy
Antibodies
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GFR
Many ways of calculating GFR
Calculation of the clearance of a substance
that is filtered and not re-absorbed by renal
tubules
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GFR 2
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Serum creatinine
Not reliable
Subjects with a low musclemass can have a normal
serum creatinine despite a
significantly reduced GFR
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The end
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