Osmolarity- Measure of the solute conc in a solution (osmoles/litre) 1osmole=

of

per

A variable osmolarity system means that we would be able to change our osmolarity. However we have constant osmolarity so increase in salt= increase in water

We consume around

more salt and water than we need to replace that lost

Must get rid of excess:

1. Volume- or else you will become oedematous and BP will

2. Water- or else you will dilute the salt in your body which will cause cells to swell

3. Salt- or you will have too high a salt level and cells will shrink

Sodium is most prevalent solute in plasma and ECF which means it's the one that has to be regulated

Water is used to regulate

Level of salt determines

Methods of water removal:

1. Skin and sweat- variable but uncontrollable- 450ml a day

2.Faeces- Uncontrollable - 100ml a day

3.Respiration- Uncontrollable 350ml/day

4. Urine- variable and controllable 1500ml/day

The minimum osmolarity of urine in humans is

The maximum osmolarity is

Water is reabsorbed throughout the kidney so all components are involved. 180L/day and 125ml/min

is absorbed before the loop of Henle

Another

is absorbed in the loop of Henle before collecting duct

Then very variable how much is absorbed in collecting duct

Loop of Henle and concentration establishment:

It can't pump water so must have gradient.

Establishing of gradient-

countercurrent multiplication system- High salt at bottom so we can have high water higher up

Descending loop of Henle is

to water

Thick ascending limb of loop of Henle is

to water but can actively pump salt outside

Urea permeability in the

of LOH and collecting duct

At first, we have plasma osmolarity fluid of

all throughout the LOH. Then salt is pumped out of the

limb to generate a 200osmolar osmotic gradient

Then fluid leaves the descending limb of LOH to establish an osmolar equilibrium between interstitial fluid and descending LOH. As a result the descending limb then becomes

After the first cycle, descending is hypertonic and ascending is hypotonic

Next important event in the cycle is that fluid enters and pushes rest of fluid around the LOH. Fluid that enters is at

and therefore more hypotonic than the fluid that is just below it- there is a gradient in the LOH and this is used to generate a gradient in the interstitial fluid

Top of ascending limb- Fluid pumps out

to generate an osmolar gradient of 200 osmoses. However it is already more

than higher up, more sodium has to be exported to generate the 200osm gradient which means we have a discrepancy between osmolarity at top and bottom of interstitial fluid

Overall osmotic gradient is established and fluid becomes

as it moves around the loop of Henle

6. Water from descending limb then equilibrates with interstitial fluid. As a result fluid at top of ascending limb is now even more hypotonic as salt has been

Permeability to urea:

Permeable to urea at

of loop of Henle and bottom of cortical

Urea concentration very high at bottom of collecting duct because we are pumping water out of collecting duct as we gradually enter more hypertonic inner medulla

Urea then leaves and enters interstitial fluid and then into the bottom of thin

limb

Then urea will cycle around the system until you reach an equilibrium which will

the osmolarity at the bottom of the medullary system

Effect of Vasa Recta:

Regulating permeability of tubular system to water is very important in controlling urine conc

If we pumped blood through the tubular system, we would eradicate the gradient we had built up as the salt would go into the

We get around this by having a blood supply completely

to salt and water that loops with the loop of Henle

Water diffuses out of the descending limb and solutes diffuse into descending limb, In the ascending limb the reverse happens

Because there is high osmolarity in the

it means that water would tend to leave the collecting duct if it was 100% permeable

Conversely if there was a really low osmolarity, it would likely mean that water would enter the collecting duct

Therefore conc of fluid that passes out of collecting duct- conc of urine- is very dependent upon there being a high medullary interstitium osmolarity

We can regulate urine production by altering permeability of

using

Aquaporin 2 molecules allow water passage

the collecting duct

Aquaporin 3/4 allow water passage

the collecting duct

These molecules synthesis are influenced by

If plasma osmolarity goes above

it triggers the release of ADH. This would be detected by

Also stimulated by a marked fall in blood volume or pressure. ADH release in inhibited by

which leads to dehydration as urine volume increases

Action of Vasopressin:

1. Blood-borne vasopressin binds with its receptor sites on

membrane of a principal cell in distal or collecting tubule

2. This binding activates

secondary messenger system within the cell

3. Cyclic AMP increases the opposite luminal membrane's permeability to H2O by promoting insertion of

water channels into the membrane. In the the absence of Vasopressin, this membrane is

4. Water enter the tubular cell from the tubular lumen through the inserted water channels

5. Water exits cell through a different water channel permanently positioned at basolateral border and then enters the blood and is reabsorbed

Overconsumption of water:

Decreased plasma osmolarity is detected by

Causes decrease in ADH secretion

Collecting duct permeability

and urne flow rate increase will cause

in plasma osmolarity

Dehydration:

Increased plasma osmolarity detected by hypothalamic osmoreceptors. Causes

in ADH secretion and thirst receptors blah de blah

Disorders of water balance:

No/insufficient production of ADH

No detection of ADH

No response to ADH

Diabetes

- Unremitting thirst, excretion of large amounts of watery urine

The greater the levels of osmoles in the ECF, the

the volume of ECF

Due to the fact that sodium is the most prevalent ion in the extracellular fluid and can therefore generate a great osmotic potential, it is is the main ion that controls volume of ECF

As a result the ability of the kidney's to control the level of sodium by excretion or reabsorption will directly influence the level of sodium in the ECF

25000mmol/l of sodium are filtered a dat whereas only

mol/l per day appear in the urine

GFR= 120ml/minx60x24= 172.8 litres per day, ECF conc of sodium= 140mmol/l

Amount filtered of sodium by kidneys a day therefore is 172.8X140= 24192mmol/l

of sodium is reabsorbed in proximal convoluted tubule

25% is absorbed in ascending loop of Henle, 8% uptake in distal convoluted tubule and 2% in collecting duct

The bulk of glomerular filtrate is reabsorbed in the proximal tubule and loop of Henle

If you want to conserve sodium the best way to do it is conserve

This helps bypass the later controlled systems. The higher the GFR, the more solutes will pass through the primary coiled tubule per minute as a result more sodium will have to be reabsorbed because of the coupling process

Receptors in the CNS that drive sympathetic activity which rescue sodium reabsorption. They contract efferent arteriole with relation to afferent arteriole

Distal nephron:

Much more active in controlling/sensing sodium levels

Low tubular Na or lower BP is detected by

cells and causes juxtaglomerular cells to release

which causes release of angiotensin II

Aldosterone is a steroid hormone produced in the

of the adrenal glands, in particular the

1. Decrease in blood pressure via baroreceptors 2. Angiotensin II release 3. Decreased osmolarity of ultra filtrate

Principal site of action for aldosterone is

and collecting ducts. Aldosterone

sodium reabsorption into the tissues

Increased potassium and hydrogen ion secretion

Steroid hormone that binds to aldosterone receptor in the cytoplasm of cells. It drives transcription of: Na/K ATPase, proteins that regulate the sodium channel and induces expression of apical Na channel of collecting duct

Diseases of aldosterone secretion:

Hypoaldosteronism- reabsorption of sodium in

nephron is reduced. Increased urinary loss of sodium and ECF volume

and increases renin, Ang II and ADH

Symptoms include: Dizziness, low BP, salt craving and palpitations

Hyperaldosteronism- Conn's disease:

Hypokalaemia, increased reabsorption of sodium, increased BP and risk of heart disease. Increased chance of oedema due to water retention

3 ways in which an increased concentration of Angiotensin II can influence renal function:

1. Vascular system- increase in

vasoconstriction and thus angiotensin II can increase BP causing an increase in GFR

2. Proximal tubule- increased sodium

and water reabsorption which increases ECF

3. Adrenal glands- increase in aldosterone synthesis

3 stimuli that lead to an increase in renin release:

1. Renal perfusion is

2. Increased renal

activity

3. Decreased levels of sodium detected by macula dense cells at top of loop of Henle

Atrial natriuretic peptide:

Small peptide made in the atria

Released in response to atrial stretch

Actions:

of renal and other systemic blood vessels, inhibition of sodium reabsorption in

and in the collecting ducts. Inhibits release of renin and

Reduces BP

Baroreceptors:

Low pressure: Atria, right ventricle and pulmonary vasculature

High pressure: Carotid sinus, aortic arch and juxtaglomerular apparatus

In the low pressure side, when there is low pressure, there is a signal through

fibres to the brain stem which leads to sympathetic activity and ADH release. When high pressure is detected, this leads to

stretch which causes ANP and BNP release

On the high pressure side, when there is low pressure, the signal is through the afferent fibres to the brain stem which causes

activity and release of

It is also detected by JGA cells which release

Small changes in Na+ will affect the amount of

produced which will in turn increase or decrease salt reabsorbed into tissues

Na levels determine the volume of ECF volume, substantial variations in Na+ result in extracellular fluid volume contraction or expansion. Reducing ECF causes blood pressure to

Reducing Na+ reabsorption reduces total Na+ levels, ECF volume and BP

The prime function of diuretics is to increase renal

In the proximal tubule, there are osmotic diuretics such as

and mannitol which give a

osmolarity so water is less likely to be absorbed into tissues

There are also carbonic anhydrase inhibitors- These block sodium from entering the cell which means that urine is less

as the hydrogen ions aren't able to leave the cell. It ensures hypertonic urine

Loop of Henle:

There are loop diuretic such as

which completely blocks the triple co-transporter of Na, Cl and K

Early distal tubule:

There are thiazide diuretics which block Na and Cl channel and also cause an increase in plasma

levels due to sodium not being able to act as a co-transporter

The daily amount of potassium filtered a day is GFR x 60 x 24 (120 x 60 x 24x10)/1000= 1728mMol/litre per day

Normally appearing in urine is 25-125mMol/litre

Movement of potassium ions under normal conditions:

After a meal potassium is absorbed which increases plasma levels of potassium, this increases the level of

, aldosterone and adrenaline. This in turn causes potassium to be taken up into tissue

Amounts filtered:

of potassium is absorbed in proximal convoluted tubule

20% is absorbed in loop of Henle and

reaches the collection duct but there is great variation in the amount secreted

Cellular mechanism of potassium secretion:

K+ secretion is stimulated by:

1. Increased plasma [K+]

2. increase in amount of

3. Increased tubular flow rate

4.

plasma pH

Potassium is secreted by principal cells and in particular potassium channels on luminal membrane

Influences on potassium secretion (and therefore excretion):

a) plasma potassium concentration- this will increase secretion of potassium into cortical collecting duct from tissues

b) An increase in aldosterone will increase potassium excretion as it is coupled to retention of

c) tubular flow rate

Flow regulates potassium by regulating intracellular calcium. Cilia measure tubular flow and calcium triggers

of potassium channels

An increase in tubular flow rate will

secretion

d) acid-base balance

Increased ph increases potassium secretion into tubular fluid

Potassium is lost after vomiting due to the fact you have depleted sodium so aldosterone will be synthesised so mor potassium will be excreted

Pair of kidneys form urine which the

carry to the urinary bladder, urine is stored in the bladder and periodically emptied through the

Kidney consists of outer, granular appearing renal

and an inner striated-appearing renal

The renal pelvis at the medial inner core of the kidney collects urine after it's formed

Kidney takes blood supply off

because it requires high pressure for ultrafiltration

Surrounded by a dense fibrous capsule- in blockage or infection , pressure builds in kidneys and they can't burst due to capsule and die

Outside is a fascial pouch containing the

Not actually fixed in position and are retroperitoneal.

Ureter on each side go to end of spinous processes

Renal stones get stuck at: ureter leaving kidney, sacral ileac joint and ureter entering bladder

On an X-ray, only stones containing

can be seen

Kidneys:

Around

long

11th and 12th rib are behind kidneys

Due to being retroperitoneal, they won't develop

Blood will come through the skin if kidney trauma is observed

Kidney is made up of different lobules. All filtration goes down to a central pyramid of

Blood supply really good in the cortex, less good in loop of Henle then even worse is later areas

Bit of kidney that dies first is

Very large vessels going straight into the kidney which rapidly branch into glomeruli capillaries

Very striated structure in kidney is

Urine is collected in major and minor

Cortex granular looking because of random organisation

Medulla striated because of radial arrangement of tubules and micro-vessels

Each lobe drains through its own papilla and calyx, kidney is made up of multiple lobes and issues can occur when these lobes do not fuse

Pelvic floor and urethra is

under voluntary control

Mechanism of urine transport:

Ureters-

Run vertically down

abdominal wall, sites of renal colic caused by kidney stones passing down them

Urine transported by

Pseudo columnar epithelium allows stretching to accommodate urine

Tight junctions are present to restrict movement of urine back into cells

Ureters and bladder-

Covered by

3-layered epithelium with slow cell turnover

Large luminal cells have highly specialised low permeability luminal membrane

Reflux of urine is prevented by action of both internal and external

of the bladder

Bladder:

Trigone of the bladder is a triangular shaped region which is formed by the two openings where the ureters enter and the internal urethral

Average volume of the bladder is around

Motor neurones that supply the external sphincter and pelvic diaphragm fire continuously at a moderate rate unless they're inhibited, keeping these muscles tonically contracted so that they prevent urine from escaping through the

It can get damaged by proximity to the vagina after

Female urethra: 4cm Male:

As it's longer it needs to generate more pressure to urinate

Prostate

in size over time which creates more of a blockage to the urethra and the bladder has to contract harder, the bladder then becomes irritable and contracts whenever it wants

Men have

sphincters - internal (involuntary) external (voluntary)

If

doesn't close then sperm ends up in the bladder

Urinary sphincters:

Sphincter vesicae-

At neck of bladder, reflex opening in response to

Controlled by

Sphincter urethrae-

In perineum

Tone maintain by somatic nerves in

nerve

Sustained closure keeps sphincter vesicle closed and reduces bladder tone

Afferent fibres from the stretch receptors carry impulses into spinal cord and eventually stimulate

supply to the bladder and inhibit motor neurone supply to

Parasympathetic stimulation of bladder causes it to contract. Changes in conformation of bladder open internal sphincter

Both sphincters are now open and urine is expelled

250-400ml can be accommodated in bladder before the tension within the walls activates

Acid: Substance that can release H+ ions in solution

Base: A substance that can accept H+ ions in solution

Buffer: A substance which can release or accept H+ ions

pH= logarithmic measurement of H+ ion concentration

Controlled pH value and its importance:

H+ is maintain in very narrow limits at low conc

Normal EC=

mol/l

This is equal to pH 7.40

Normal plasma pH range is 7.34-7.45

Outside pH range of 7.2 and 7.6 is serious condition

Urine pH range is from

to 8.5

Control of pH is dependent on dissociation of hydrogen bicarbonate involving the enzyme

pH is dependent on H+ conc and bicarbonate ion concentration

To determine this we use

equation:

pH= pKa+log(HCO3-)/aPCO2

Metabolic reactions are highly sensitive to pH or ion concentration

Acid-base regulation and cellular buffer system:

Basic steps:

1. Extracellular and intracellular buffers

2. Control of partial pressure of CO2 in blood by alterations in rate of

3. Control of plasma HCO3 conc by changes in renal

excretion

Buffering process:

Principle buffer in the blood is H2CO3<-> H++HCO3-

Principle buffer in

is H2PO4 <-> H+ + HPO4^2-

In metabolic acidosis. around

of acid load is buffered in cells

In metabolic alkalosis, only 30% of OH- load is buffered in cells.

In respiratory acidosis/alkalosis, all buffering is

The most important EC buffering system is:

- H+ + HCO3- <-> H2CO3 <-> H2O + CO2

- HCO3- is independently regulated by

excretion

PCO2 is also independently regulated by change in rate of alveolar ventilation

Buffering at a local level:

H2SO4 and HCl are produced during metabolism but don't circulate as free acids

They are immediately buffered in the ECF by

These reactions minimise increase in EC H+ but excess must be excreted by kidney to prevent depletion of HCO3

Hydrogen ion excretion:

Sources of H+ ions in body-

Physiologically- carbohydrates + fats, sulphur-containing amino acids, arginine, histidine and lysine

Pathologically-

, carbohydrates + fats, diabetes and ketoacids

Volatile acids- produced from metabolism of carbohydrates + fats, result in carbon dioxide production which is lost through respiration

Renal H+ excretion-

Kidneys must excrete 50-100mmol of non-carbonic acids generated each day

It involves different mechanisms at various parts of the nephron

Overview: All

ions filtered into the urine are reabsorbed

Secreted H+ ions are then excreted with: filtered buffers e.g. phosphate and creatinine or manufactured buffers

Renal H+ pumps-

In the PCT, ions are secreted into the lumen by the

exchanger

Bicarbonate ions are then returned to the circulation by the Na/HCO3 cotransporter

In the collecting duct, the luminal pump is mediated by active H+ ATPase and Cl-HCO3 exchanger is basolateral membrane

Net effect is excretion of 1H+ + addition of 1HCO3- to the plasma

Regulation of excretion-

To increase or decrease H+ secretion there are primary and secondary mechanisms

To increase-

Primary- decrease plasma

concentration and increase pp of

Secondary-

filtered load of bicarbonate, decrease ECF volume, increase ang II and

aldosterone + hypokalaemia

To decrease H+ secretion, it's the opposite

Bicarbonate reabsorption:

is reabsorbed in the PCT with the remaining being absorbed in the thick loop of Henle and outer medullary collecting duct- segmental reabsorption

New bicarbonate formation-

Reason for new formation= bicarbonate reabsorption is

bicarbonate lost during buffering of non-volatile acids

In the liver, amino acids are broken down into

and urea, the first product is converted to ammonium ions and alpha-ketoglutarate in the kidney

Ammonium excretion-

Ability to excrete H+ ions as ammonium adds important degree of flexibility to regulation

Basic acid-base disorders:

Metabolic acidosis-

plasma pH and

HCO3-. It is caused by:

Addition of non-volatile acids (ketoacidosis in diabetes)

Loss of non-volatile alkalis e.g. diarrhoea

Failure to reabsorb sufficient

e.g. renal failure

Respiratory compensation occurs by raised ventilation due to peripheral chemoreceptor stimulation

Renal excretion of net acid increases

Metabolic alkalosis:

plasma pH and HCO3-

Caused most commonly by loss of non-volatile acid e.g.

Also caused by raised

Compensation occurs by:

Reduced ventilation: pCO2 rises by 0.7mmHg for every 1mmol/l rise of plasma HCO3-

Renal excretion of excess HCO3- but this can be limited if low blood volume with Na+ and Cl- depletion

Respiratory acidosis:

Low plasma pH and high

Caused by reduced alveolar ventilation or impaired gas diffusion

Renal compensation occurs by increasing HCO3- and NH4+ secretion

Respiratory alkalosis:

High plasma pH and reduced pCO2

Caused by increased

Renal compensation occurs by decreasing HCO3- reabsorption and NH4+ secretion

Glomerular filtration- Formation of an ultra filtrate of plasma in the glomerulus

Kidney failure is failure of

Passive process: ATP isn't involved but fluid is driven through semipermeable walls of glomerular capillaries into

by hydrostatic pressure of heart

The fenestrated endothelium of capillaries and semipermeable Bowman's capsule is highly permeable to small solutes and

It is impermeable to cells, proteins and drugs etc

Ultimately produces a

Concentration of solutes is same as in plasma, Peas and salty water analogy

Tubular systems are regulatory- have

systems to alter conc of solutes to what the body wants.

Glomerular filtration pressures:

Driving force-

in glomerular capillaries. (Pgc) Opposing pressure- hydrostatic pressure of

(Pt) and

pressure of plasma proteins in glomerular capillaries (Pigc)

Ultimately there is a net ultrafiltration pressure of

Puf=Pgc-Pt-Pigc

Glomerular filtration rate:

GFR=Puf X Kf - Kf is an ultrafiltration coefficient

Any changes in filtration force of kf will result in GFR imbalances. Kidney disease may reduce number of functioning glomeruli leading to reduced

leading to reduced Kf. Dilation of glomerular arterioles by drugs/hormones will

Kf

GFR: Amount of fluid filtered from glomeruli into Bowman's capsule per unit of time

GFR depends on number of factors:

Pgc, Pigc, Pt and Kf

Autoregulation of GFR:

Autoregulation fluid and solute excretion remains relatively constant.

Increase in GFR will constrict

and dilate

arteriole whereas decrease in GFR will do the

Mechanisms of autoregulation:

1. Myogenic mechanism

Vascular smooth muscle constricts when

It keeps GFR constant when blood pressure rises. When arterial pressure rises, the

arteriole stretches and the contracts

2. Tubuloglomerular feedback

Macula densa in distal convoluted tubule but very close, increased filtration means more

will go through. This can be detected by macula dense releasing a signalling molecule to afferent arteriole and causes it to constrict reducing filtration-

Events affecting GFR:

Severe haemorrhage causes GFR to

Obstruction in nephron tubule causes GFR to

Reduced plasma concentration causes GFR to

Small increase in blood pressure causes GFR to

Renal blood flow:

Approx

1/5 of cardiac output. Renal plasma flow- approx

Filtration fracrtion= 0.2 (ratio between RPF and amount of filtrate filtered by glomerulus which is normally 20%

GFR=

GFR=RPF X FF

Concentration won't change but the amount will

Renal clearance:

The number of litres of

that are completely cleared of the substance per unit time

C= (U X V)/P in ml/min

U=

P=

V= rate of urine production

If a molecule is freely filtered and neither reabsorbed nor secreted in nephron so amount filtered equals amount excreted. GFR can be measured using

of this molecule

Inulin-

Plant polysaccharide, freely filtered and neither reabsorbed nor secreted, not toxic and measurable in urine and plasma

Gives a clearance of

which is GFR for average adult

Values for renal clearance:

Na- 1ml/min K- 11ml/min Ca-1.8ml/min Mg 3.6ml/min Phosphate- 6.4ml/min Glucose-0.05ml/min Urea- 17ml/min

Renal plasma flow:

Measured by PAH (paraaminohippurate) clearance= 625ml/min

Clearance rate is

Amount cleared of this substance is all of the plasma. Measurement of this substances clearance is the renal plasma flow. Filtered and actively secreted in one pass of kidney

Clearance, reabsorption and secretion:

Amount go substance appearing in urine reflects combined effects of filtration, reabsorption from nephron tubule and secretion from blood into tubular fluid such that: Amount excreted=

If GFR falls, excretory products

in plasma. Can affect how drugs are used and metabolised

Method of concentration water and excreting products, urine is main method of controlling loss of water and balance of sodium, potassium and hydrogen

Functions of the kidneys:

Maintaining

balance in the body

Maintaining proper osmolarity of body fluids, primarily through H2O. Function is important to prevent osmotic fluxes into or out of cells, which could lead to detrimental swelling or shrinking of cells

Regulating quantity and concentration of most ECG ions, including sodium, chloride, potassium, calcium, hydrogen, bicarbonate, phosphate, sulphate and magnesium

Maintaining proper plasma

- important in long term regulation of arterial blood pressure. Function is accomplished through the kidney's regulatory role in salt and H2O balance

Helping maintain proper acid-base balance of body by adjusting urinary output of

Excreting the end products of bodily metabolism such as urea, uric acid, creatinine, bilirubin and hormone metabolites

Excreting foreign compounds

Producing

Producing

-an enzymatic hormone that triggers a chain reaction important in salt conservation by kidneys

Converting vitamin

into its active form

Mechanism of urine production in kidneys:

Filtration-

Blood passing through

is filtered, filtrate consists of all components, the bowman's capsule is the thing on the outside

Reabsorption-

Material to be retained is reabsorbed in

includes ions, glucose, amino acids, small proteins, water etc

Creation of hyper-osmotic extracellular fluid-

Main function of

and vasa recta, counter current mechanism

Adjustment of ion content of urine-

Principally a function of

controls amount of Na+, K+, H+, NH4+

Concentration of urine-

Occurs at collecting tubule, movement of water down osmotic gradient into ECF

Controlled by

Structural organisation of kidney- DIAGRAM

Structure of a nephron- DIAGRAM

Function of parts of nephron:

Vascular component-

The afferent arteriole carries blood to the

which is a tuft of capillaries that filters a protein-free plasma into the tubular component.

The efferent arteriole carries blood from the glomerulus

Perittubular capillaries supply the

, it is involved in exchanges with the fluid in the tubular lumen

Tubular component-

Bowman's capsule- collects the

Proximal tubule- Uncontrolled reabsorption and secretion of selected substances

Loop of Henle - Establishes an

in the renal

that is important in kidney's ability to produce urine of varying concentration

Distal tubule and collecting duct- variable, controlled reabsorption of Na+ and H2O and secretion of K+ and H+ occur here

Structures separating glomerular capillary plasma from fluid in Bowman's capsule:

Afferent artery is much bigger than efferent which means there is a pressure gradient, fenestrated capillaries act as a sieve.

cover all the capillaries with a discontinuous capillary structure

Filtrate enters proximal tubule

The fluid must pass through 3 layers of glomerular membrane: 1.

2.

3.

Renal corpuscle:

Components-

Bowman's capsule, glomerulus and podocytes associated with glomerulus

Blood supply-

At vascular pole of corpuscle, from afferent arteriole, exit efferent

Filtration barrier consists of-

fenestrae in capillary endothelium, specialised basal lamina, filtration slits between foot processes of

allows passage of ion and molecules

Drainage of filtrate-

urinary pole of corpuscle, drains to

Proximal convoluted tubule:

Functions-

Reabsorption of

of glomerular filtrate, NA+ uptake by basolateral pump, water and anions follow Na+

Glucose uptake by Na+/glucose co-transporter and amino acids by co transporter, protein uptake by

Structural features-

epithelium, sealed with tight junctions, membrane area increased to maximise rate of reabsorption

Contains

- membrane protein mediating transcellular water diffusion, prominent mitochondria reflect high energy requirement

Loop of Henle:

Works 3x to concentrate fluid, descending limb is quite thin

Descending thin tubule-

Passive osmotic equilibrium and

epithelium

Ascending thick limb-

Na+ and Cl- actively pumped out of tubular fluid, very water-impermeable tight junctions, membranes

aquaporins, results in hypo-osmotic tubular fluid,

epithelium and high energy requirement

Vasa recta-

Blood vessels also arranged in loop, blood in rapid equilibrium with ECF

Distal convoluted tubule:

Expect to see

Deals with small volumes of fluid, interdigitations- deep clefts in the border where lots of interactions occur, site of osmotic

Adjustment of Na/K/H/NH4+ - control by

cuboidal epithelium, few microvilli, couple lateral membrane interdigitation with Na pumps, specialisation at

Medullary collecting duct:

Passive mechanism of water reabsorption, tight junctions are impermeable but have

for water absorption, passes through medulla with its hyper osmotic extracellular fluid. Rate of water movement depends on

in apical membrane, content varied by exocytosis/endocytosis mechanism. Under control from the pituitary hormone

Basolateral membrane has aquaporin-3 not under control

Juxta-glomerular apparatus:

Juxta-glomerular cells are around the afferent arterioles, produces

that controls blood pressure, it's not particularly active as it relies on hormones so won't acutely change blood pressure, think ACE inhibitors. Cellular components are- macula densa of

and juxta-glomerular cells of

Loss of excretory function--> accumulation of waste products

Loss of homeostatic function-> disturbance of electrolyte balance

Loss of acid-base control

Loss of endocrine function

Causes:

Lethargy and anorexia-

accumulation of nitrogenous waste products, hormones, peptides and other middle sized products, acidosis, hyponatraemia, volume depletion and

Salt + water imbalance-

Inability to

sodium excretion when sodium depleted

Osmotic diuresis- caused by high concentration small MW products

Inappropriately high loss of salt and water results in volume depletion which causes

BP. Salt and water loss usually found in patients with tubulointerstital disorders in which concentrating mechanisms have been damaged

It is more usual for patients with renal dysfunction to have difficult in excreting salt and water. This leads to a tendency to retain sodium- hypertension, oedema and pulmonary oedema

Implications of acidosis:

Caused by decreased excretion of

ions and retention of acid bases

Buffered by H+ ions passing into cells in exchange for K+ ions- therefore aggravates tendency to hyperkalaemia

Another complication is increasing CO2 loss through the lungs-

-air hunger

Exacerbates anorexia and muscle catabolism

Hyperkalaemia:

Caused by failure of

to secrete potassium

Exerted by acidosis- causes shift of potassium from intracellular to extracellular space. Can cause

Clinical features of hyperkalaemia are dependent on the chronicity of hyperkalaemia

Metabolism:

Decreased erythropoietin production in renal failure results in

Low 1-25 vit D levels result in poor intestinal calcium absorption, hypocalcaemia and hyperparathyroidism

Increased cardiovascular risk

Difference between acute or chronic loss of function of function:

In acute, renal size is

whereas with chronic, renal size is

And with acute, there is normal

but its abnormal in chronic

Treatment/management:

Initial management-

intravenous normal saline to correct fluid depletion, intravenous sodium bicarbonate to correct

intravenous insulin and dextrose to lower plasma potassium

Assessing GFR:

Urea- poor indicator, confounded by diet, catabolic state, GI bleeding, drugs etc

Creatinine- Affected by muscle mass, age, race, sex etc. Need to look at patient when interpreting the result

Estimated GFR- Equation which automatically calculates from serum

Easiest equation uses age and ethnicity

Alternatives can include weight, albumin etc

Inulin clearance

Long-term management:

GFR measure, remains on regular haemodialysis, low potassium diet and fluid restriction, erythropoietin injections to correct anaemia

On average we consume

more water and salt than we need to replace that is lost

Ideal solution would be to pump everything into the bladder ad excrete it, this isn't a problem for ions but is impossible for urea and water

We produce urine by

through a molecular sieve but we can't afford to lose all of the water and small molecules that pass through the filter

We need to reabsorb 99% of ultra filtrate reabsorbed

Need to maintain solute balance, plasma concentration and pH

Osmolarity- Measure of osmotic pressure exerted by a solution across a

membrane

Each ion is taken by itself and charge doesn't have any extra effects

Main regulator of plasma osmolarity is

Specialisation along the tubule allows reabsorption and secretion. All this goes on across the renal tubular wall

Transcellular transport refers to the transport of a substance across an epithelium by passing

the cell

Paracellular transport means that a substance passes

cells to be transported across the epithelium

Types of transport in the tubules:

Processes that can be the most regulated are osmosis, active processes and counter/co-transport

Passive movement:

Protein independent transport-

molecules- solute concentration to rate is linear

Protein dependent transport-

molecules - linear than quickly horizontally asymptomatic

Active movement:

Water transport- water

go straight through the membrane

Protein reabsorption- Protein binds to receptor which will be internalised, receptor is returned to cell surface, vesicle is dissolved and protein is in cell

Transport maxima- We can reabsorb normally all of the glucose- however it can be exceed

Most of the noradrenaline transports are located in the

Active sodium transprot- reabsorption of water- READ NOTES

Main routes for NA+ entry into tubular cells in the thick ascending limb of the loop of Henle, in the distal convoluted tubule and in the principal cels in the cortical collecting tubule:

Descending limb which allows passive reabsorption, not a lot of

fairly simple cells no mitochondria

Thick ascending limb more cilia and mitochondria which actively exports

- Cells have very tight epithelial cells

- By now 85% of water and 90% sodium and potassium have been reabsorbed into tissue- therefore tubular fluid leaving is

Chloride reabsorption is linked to sodium is dependent upon pumping in sodium

Calcium is absorbed by sodium exchange system

Thiazides cause a

Distal part of distal convoluted tubule and cortical collecting duct:

DCT- Sodium reabsorbed

CT- Sodium reabsorbed

Conditions:

Renal tubule acidosis- blood is acidic

Bartter syndrome:

Severe

Moderate metabolic alkalosis

Hypokalaemia

Excess secretion of

Na, CL, K transporter isn't working properly

May be due to a problem in the potassium channel as you need enough potassium in the lumen to allow

back in

Fanconi syndrome:

excretion of low MW protein

excretion of uric acid, glucose, phosphate into

Chloride transporter influences endosomal transport, difficulty with transporting proteins onto cell surface to reabsorb glucose

Bowman's capsule- osmolarity is

blood osmolarity

End of proximal tubule- About 65% of all solutes are absorbed, water moves via osmosis to maintain osmolarity

Emerging from loop of Henle-

hypotonic due to NaCl being pumped out of the ascending limb

Excretion means into

Secretion means into