Kidneys

Sherif Elsobky MB 5

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

Topic to cover Anatomy The nephron Hormones Acid base Clinical

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

Renal functions
Impressive organ for its size! ABCDEF
Acid-base Blood pressure Ca D vitamin EPO Filtration

External Anatomy
External kidney Renal fascia: Most outer layer of connective tissue, connects kidneys to abdomen Adipose capsule: Cushing's the kidneys Renal capsule: Smooth connective tissue Blood supply Renal artery AA Renal vein IVC

Internal Anatomy
Inner Kidney 1) Ureters 2) Renal pelvis 3) Renal cortex 4) Renal medulla 5) Renal pyramid 6) Renal column 7) Renal papilla 8) Minor calyx 9) External capsule

Which structures from previous slide would be visible on an intravenous urogram/pyelogram?

Blood supply

Aims

Anatomy

The nephron
Hormones Acid base Clinical

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.

The Nephron
Branch of renal artery Bowmans capsule Glomerulus Proximal convoluted tubule Distil convoluted tubule Collecting duct Loop of Henl Capillary

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

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

Which part of the nephron is impermeable to water?

The nephron osmoregulation

Collecting duct

Loop of Henl

More and more salty

H2O H2O

Na+ Na+ Na+

H2O H2O H2O

H2O H2O H2O

Freely permeable to water

Impermeable Variable permeability to to water water

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 afferent arteriole and drained by an efferent arteriole Two cellular layers separate the blood from the glomerular filtrate in Bowmans capsule: The capillary endothelium and the specialized epithelium of the capsule

Properties
Glomerular capillaries are 50x more permeable than skeletal muscles Capillary walls are one cell thick They are pierced with fenestrations Proteins do not pass (due to basal lamina layer and negatively charged properties due to sialoproteins (repels albumin)

Bowman's capsule

Questions commonly asked about Bowmans capsule

Label Bowmans capsule What are the properties of Bowman's capsule Explain the mechanism of ultrafiltration

Bowman's Capsule
Functional anatomy Fenestrations of glomerular endothelial cells allows for a greater function of filtration fraction Basal lamina and pedicles prevents filtration of larger proteins

Podocytes
Function of podocytes? Mechanical support to filtration membrane

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

Glomerular filtration
Blood enters the glomerulus from RA Resistance of efferent arterioles greater than the afferent arterioles

This produces a high pressure gradient that leads to ultrafiltration of plasma through the bowman's capsule
Osmotic pressure of plasma proteins (oncotic pressure) opposes filitration

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 of creatinine per unit time
useful measure for approximating the GFR

What factors influence GFR ?

Answers:

Blood pressure Renal blood flow Obstruction to urine outflow Loss of protein-free fluid Hormones: Renin, Aldosterone, ADH, ANP

Kidneys retain Na HCO3 Water Glucose

PCT
Made up of a single layer of cells that are united by apical tight junctions Luminal edges of the cells have striate brush border due to the presence of many microvilli

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 the tubules Reabsorbed molecules pass into the surrounding capillaries

Na+ reabsorption
Electrolyte and water homeostasis Absorbed through cotransport and exchange mechanisms with other substances e.g. H+, glucose, Cl etc 60% of Na+ is absorbed at PCT via NA-H exchange 30% through Na-2Cl-K co-transporter in thick ascending loop of Henle Usually an active process Remember that two mechanisms are needed: 1) From lumen to inside the cell through apical membrane 2) Intra-cellular to interstitial fluid via basolateral membrane (usu Na+/K+ exchange

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

 Thou sodium goes, water shall follow

Sherif Elsobky

Loop of henle physiology

1. The descending limb is impermeable to ions but premable to H20

2.
3.

The ascending limb is impermeable to H20 but not to ions

Na-K-2Cl co-transporter actively transports solutes from the thick ascending limb (or passively in thin section) into interstium 1. This is the co-transporter furosemide acts on

4. 5.

Water moves through the descending limb via osmosis Urea which was absorbed into the medullary interstium from the collecting duct, diffuses into the ascending limb (this helps to concentrate urine) and lowers water potential Interstitial fluid diffused into the vasarecta which prevents an equilibrium from forming

6.

The aim of the loop of Henle is to create a hypertonic environment in the renal medulla to allow re-absorption of water from the collecting duct thus concentrating the urine.

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

Counter-current mechanism
1. The fluid in the tubule become hypotonic as it moves down the descending limb 2. Hypertonic in ascending limb 3. Vasa recta absorbs interstitum fluid(to prevent equilibrium formation) 4. This produces a countercurrent mechanism which allows the formation of concentrated urine 5. The longer the loop of Henle the more concentrated the urine AIM IS TO PRODUCE HYPERTONIC URINE!

DCT and collecting ducts

DCT: Na-CL transporter, CL leaks through channels 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

Aims
Anatomy The nephron

Hormones
Acid base Clinical

Macula densa
Area of closely packed specialized cells lining the wall of the DT Sensitive to the concentration of NaCl in the DCT A decrease in NaCl conc initiates a signal from the macula densa that has two effects: Decreases resistance to blood flow in the afferent arterioles Increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles

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

RAAS

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

ADH mode of action

Aldosterone
Stimulated by ACE II, ACTH, K+ Released from zona glomerulosa layer (most outer layer) of adrenal glands + mineralocorticoid receptor within the principal cells of the DT & CD to up regulate Na+/K+ receptors Clinical:
Spironalactone Conns syndrome

EPO

Vitamin D Cycle

Aims
Anatomy The nephron Hormones

Acid base
Clinical

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

What you need to know??

PCT cells contain Carbonic anhydrase which converts CO2 +H20 H2CO3 H2CO3 basically becomes divorced (H+ and HCO3) and goes into separate directions H+ goes through the apical membrane though Na-H exchange 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)

 Ammonium (NH4) is produced predominantly within the proximal tubular cells. The major source is from glutamine Ammonium is produced from glutamine by the action of the enzyme glutaminase. Ammonium is a buffer

 The majority of H+ in PCT becomes CO2 and water In DCT, CD:

H+ + NH3 NH4 HPO4 + H H2PO4

Urine pH varies from 4.5-8

Aims

Anatomy The nephron Hormones Acid base

Clinical

Renal failure
Acute vs Chronic Pre-renal, renal and post-renal failure Investigations

5 stages of CKD

Acute vs Chronic
Can sometimes be difficult to differentiate In chronic patients tend to have: Less symptoms Smaller kidneys Anaemia Low Ca2+ Hypertension

Aetiology
The surgical sieve Infectious Autoimmune Vascular Malignant Iatrogenic Traumatic/mechanical Metabolic Inflammatory Inherited Idiopathic

Diuretics
Mechanisms Which area of the nephron they act Side effects

How does Furosemide work and list two side effects? (5 marks)
Loop diuretic Ascending limb of loop of Henle Na-K-2Cl symporter antagonist Side effects:
Hypotension Hypokalemia Ototoxic

Diuretics

Examples of diuretics
Carbonic anhydrase inhibitors: Acetazolamide Loop diuretics: furosemide, torasemide Thiazide diuretics: bendroflumethiazide Potassium-sparing: Spironalactone/eplerenone Osmotic diuetics: Mannitol

Common investigations
Bloods: FBC (anaemia), U&Es, Ca++ GFR. Urinalysis: is a simple means of assessing for renal disease. ABGs: helps identify acid-base concerns. Imaging: Ranges from ultrasound to arteriography and can uncover many pathologic events Kidney biopsy Antibodies

GFR
Many ways of calculating GFR Calculation of the clearance of a substance that is filtered and not re-absorbed by renal tubules

GFR 2

Serum creatinine

Not reliable Subjects with a low muscle mass can have a normal serum creatinine despite a significantly reduced GFR

The end

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