Kidneys Online

8/2/2019 Kidneys Online

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Kidneys

Sherif Elsobky

MB 5


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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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