leanne (L1-2)

Question 1

Renal function and contribution to homeostasis

Answer 1

Blood ionic composition
Blood pH
Blood Volume 
Blood Pressure
Blood osmolarity (concentration of solutes)
Excretion of waste 
Hormone production
Glucose levels

Question 2

diseases from extreme body fluid volume

Answer 2

HYPOVOLAEMIA
too little body fluid vol
dehydrated

HYPERVOLAEMIA
too much body fluid vol
fluid overload

SYMPTOMS AND SIGNS L1 S6

Question 3

define JVP and oedema

Answer 3

JVP - jugular venous pulse / pressure

Oedema - tissue swelling (peripheral, pulmonary, ankles etc)

Question 4

Regulation of fluid balance

Answer 4

Kidneys play major role in regulating body fluid homeostasis

Regulate both volume and composition

Kidneys do this by altering volume and composition of plasma, which in turn influences the other fluid compartments

Maintenance of volume linked to regulation of extracellular sodium and water – this in turn controls blood pressure.

Question 5

define

• osmolarity
• osmotic pressure
• oncotic pressure
• hydrostatic pressure

Answer 5

OSMOLARITY - the measurement of solute concentration or osmotically active solutes = osmoles (osmol/L) or (Osm/L) or (mOsm/L)

OSMOTIC PRESSURE - The pressure which needs to be applied to the solution to prevent an inward movement of fluid across a semipermeable membrane.
High osmolarity = high osmotic pressure (strong inward pull on water).

ONCOTIC PRESSURE / COLLOID ONCOTIC PRESSURE - The osmotic pressure exerted by the proteins in the blood plasma or exudate/filtrate which attracts/pulls water into that compartment.

HYDROSTATIC PRESSURE - The force exerted by a fluid against a capillary wall.

Question 6

Tonicity and osmolarity

Answer 6

cell in hypo-osmotic solution
water will move into the cell
low osmotic pressure outside the cell (high in cell)

cell in iso-osmotic solution
water will be balanced, no net movement
high osmotic pressure in and out of cell

cell in hyper-osmotic solution
water will move out of the cell
very very high osmotic pressure out of the cell (high in the cell)

Question 7

if Pc > osmotic pressure

Answer 7

so fluid will leave the capillary promoting filtration of the plasma.

bottleneck effect in capillary –> wide afferent / narrow efferent
HIGH HYDROSTATIC PRESSURE IN CAPILLARY
LOW OSMOTIC PRESSURE IN TISSUE

Question 8

if Pc < osmotic pressure

Answer 8

so fluid will leave the capillary still

bottleneck effect is lower but still pushes water through
LOW HYDROSTATIC PRESSURE IN CAPILLARY
HIGH OSMOTIC PRESSURE IN TISSUE

Question 9

STRUCTURE OF KIDNEY

Answer 9

DIAGRAM IN L1 S12

Question 10

NEPHRON - FUNCTIONAL UNIT

Answer 10

DIAGRAM IN L1 S13

- renal corpuscle
bowman's capsule
glomerulus
- renal tubule
proximal convoluted tubule (PCT)
loop of henle
distal convoluted tubule (DCT)

several nephrons empty into the collecting duct
several collecting ducts converge into the papillary duct - minor calyces

Question 11

JUXTAMEDULLARY NEPHRON

Answer 11

DIAGRAM L1 S14

Cortical nephrons are much shorter than the juxtamedullary nephrons
So C nephrons don;t play a role as important in altering the outputs

Loop of henle helps to conc the urine composition output
THIN descending limb and THICK ascending limb

Question 12

FUNCTIONAL OVERVIEW - STEPS THROUGH THE NEPHRON

Answer 12

FILTRATION
Filtration under pressure – water & blood plasma solutes = Glomerular Filtrate. (GFR =180 L/day 125 mL/min)

TUBULAR REABSORPTION
99% of water and many solutes – reabsorbed back into the blood via passive and active processes (Glucose, Amino acids, Urea; Ions - Na+, K+, Ca2+ , Cl-, HCO3- and HPO42-

TUBULAR SECRETION
Renal tubule and duct cells secrete wastes, drugs, excess ions etc. out of the blood into the filtrate

URINE EXCRETION
Renal tubule and duct cells secrete wastes, drugs, excess ions etc. out of the blood into the filtrate

Question 13

bowman’s capsule structure

FUNCTIONS OF : mesangial cells / parietal layer / visceral layer

Answer 13

DIAGRAM IN L1 S16

Mesangial cells are smooth muscle cells (around vasculature and around afferent arteriole)
They contract and impact the diameter and SA available for filtration
They contract vasculature and change hydrostatic pressure

Parietal layer - outer squamous epithelial cell of the bowman’s capsule

Visceral layer - made out of podocyte cells which have digits that can lock in and create another filter … BEAUTIFUL

Question 14

describe the feedbakc mechanisms of the bowman’s capsule

Answer 14

Cells from the afferent arteriole, called juxtaglomerular cells, are touching the macula densa cells of ascending limb - very important because they create juxtaglomerular apparatus (she says juxtamedullary though)

This is a feedback mechanism

• macula densa cells act as chemoreceptors, they detect the amount of sodium chloride in the filtrate
• juxtaglomerular cells act as mechanoreceptors, they detect stretch in capillary wall

We now have mechanisms to detect conc of the filtrate and blood volume
Both mechanisms manage glomerular filtration rate (GLR)

Question 15

glomerular filtration - what 3 characteristics allow the filtration?

Answer 15

1 – FENESTRATIONS
they are pores in the glomerular endothelial cells that prevent filtration of blood cells but allows all components of blood plasma to pass through.
Fenestrations 0.07 – 0.1µm diameter , everything but RBC and platelets.

2 – BASAL LAMINA
prevents filtration of larger proteins
BL negatively charged prevents large negatively charged molecules.

3 – SLIT MEMBRANE BETWEEN PEDICELS
this prevents filtration of medium-sized proteins
Spaces between pedicels = Filtration slits covered by membrane allow molecules less than 0.006 – 0.007µm in diameter e.g. water, glucose, vitamins, ammonia, urea, ions small plasma proteins and some albumin.

Question 16

define filtration and which membranes/pressures allow it to happen

Answer 16

The use of pressure to force fluid through a membrane.
The difference between the forces that promote filtration and the pressures that oppose filtration.

This happens to a greater extent in the renal corpuscle than any other capillary bed of the body. – Why?

• Large surface area of glomerular capillaries – regulated by mesangial cells.
• Endothelial membrane is thin and fenestrated ~50X leakier than other capillaries.
• Blood pressure is much higher owing to the differences in diameter of afferent and efferent arterioles.

Question 17

NFP definition and equation

Answer 17

NFP = GBHP - CHP - BCOP

nfp - net filtration pressure (the totla pressure that promotes filtration
gbhp - glomerular blood hydrostatic pressure Pgc
chp - capsular hydrostatic pressure Pbc
bcop - blood colloid osmotic pressure πgc

Question 18

Three mechanisms control GFR:

Answer 18

1. Renal Autoregulation a) Myogenic and b) Tubuloglomerular feedback
2. Neuronal regulation
3. Hormonal regulation

These work in two different ways:

1. Adjustment of blood flow into and out of the glomerulus
2. Alteration of glomerular capillary surface area

Question 19

Renal autoregulation - MYOGENIC MECHANISM

Answer 19

Maintenance, by the kidneys themselves, of a constant renal blood flow and GFR in response to everyday alterations in blood pressure.

Myogenic Mechanism - in response to ↑BP and ↑GFR
Myogenic autoregulation - rapid, musculature, increase in blood pressure

↑ BP stretches the walls of the afferent arterioles
JG Smooth muscle fibres contract
Narrowing the lumen of afferent arteriole
↓renal blood flow and GFR

In response to ↓BP and GFR the opposite happens

Question 20

Renal autoregulation - TUBULOGLOMERULAR FEEDBACK

Answer 20

Negative feedback regulation via Macula densa cells. Slower mechanism.

↑flow of filtrate into renal tubules (fast).
↓reabsorption of ions and water
Sensed by JGA - ↓NO release
Afferent arterioles constrict
 ↓in blood flow and GFR

Question 21

role of juxtaglomerular apparatus

Answer 21

JUXTAGLOMERULAR APPARATUS DOES 2 THINGS

• Secretes ?, this is the long distance hormonal effect
• Decreases its secretion of nitric oxide (vasodilator), this is the local effect

Local effect of it in the kidney will allow the efferent arteriole to constrict - will remove the vasodilatory impact and allow the decrease in blood flow through glomerulus and decrease in GFR

Question 22

Substances filtered/reabsorbed and excreted

Answer 22

TABLE IN L1 S26

Question 23

water reabsorption

Answer 23

Most water reabsorbed in proximal (convoluted) tubule and Loop of Henle

Fine tuning and hormonal regulation of water reabsorption occurs mainly in (medullary) collecting ducts

Water reabsorption from collecting ducts is passive & if we want to concentrate urine requires :

1. Insertion of water channels (aquaporins) - regulated by antidiuretic hormone (ADH)
2. An osmotic gradient - generated by the countercurrent system in loop of Henle

Question 24

1. Glucose reabsorption in the PCT

Answer 24

Reabsorption of glucose through sodium glucose transporters (SGLTs)

At normal levels of plasma glucose, all glucose in the filtrate is reabsorbed via the PCT

It is co-transported with Na+ at the luminal membrane by a Na+/glucose cotransporter

It then diffuses from the cell into the interstitial fluid then into the peritubular capillaries

Question 25

2. Reabsorption of sodium ions and secretion of hydrogen ions in PCT

Answer 25

In the PCT, we can reabsorb Na ions back into the blood and get rid of H+ ions So we can secrete it into the filtrate - which helps us with buffering CO2 in H2O in association with carbonic anhydrase = carbonic acid H2CO3 Broken down into a H ion which will will be pushed into the Na/H antiporter Na+ comes in to give us gradients for other mechanisms We can get rid of our bicarbonate which can then get reabsorbed (and we can pump out Na) Na reabsorbed from surrounding tissues back into the blood Get rid og H ions by secreting it back into the filtrate

Question 26

3. The distal part of the PCT is involved in passive reabsorption of certain ions and urea

Answer 26

A lot of passive diffusion down conc gradient | Cells are leaky - pericellular movement (between cells) and transcellular movement (through linked channels)

Question 27

4. Reabsorption in the Loop of Henle

Answer 27

The descending limb is permeable to water (15%) The ascending limb is impermeable to water but cells have Na+ - K+ - 2Cl- symporters in the apical membrane

Question 28

5. Reabsorption and secretion in the DCT and CD

Answer 28

The amount of water and solute reabsorption in the late DCT and CD varies depending on the body’s needs. Water - heavily influenced by the action of Anti Diuretic Hormone (Arginine vaspressin)

Question 29

Control of ADH release

Answer 29

Low pressure sensors in atria, pulmonary vasculature High pressure sensors in carotid sinuses & aortic arch Stretch receptors in afferent arterioles (indirect via release of angiotensin II) ↓ pressure/stretch → ↑ADH IN HYPOTHALAMUS - we have detectors as osmoreceptors and the thirst center (which has msgs coming into it as a result of cellular dehydration) ON PERIPHERY - extracellular dehydration (plasma and interstitial fluid) Low plasma volume - can be detected by pressure sensors (can detect high/low pressures and can send signals to the hypothalamus)

Question 30

ADH | where is it made? how is it transported? its 2 functions?

Answer 30

Produced in supraoptic & paraventricular nuclei of hypothalamus Transported to the posterior pituitary Short plasma half life. TWO main functions:- - Reduce water excretion (antidiuretic) - Stimulate vasoconstriction We get messages from osmoreceptors/thirst centers etc It talks via the paraventricular neuron and supraoptic neuron Will secrete the ADH from the posterior lobe of the pituitary This will travel via the circulatory system and will bind to receptors and the principal cells of the collection duct

Question 31

ADH mediated AQP2 export to the apical membrane

Answer 31

We have our vasopressin 2 receptor and our vasopressin adh (also called arginine vasopressin) It binds and we have a CAP dependent system where it leads to the activation of PKA Leads to the phosphorylation of our proteins within a vesicle Leads them to be shuttled to the apical membrane of the cell Which inserts the aquaporins We also have aquaporin 3 expressed on the basal lateral Which means we now have a transcellular pathway (from tubule fluid, through the cell, into the interstitial fluid, and into the vasculature)

Question 32

urine production

Answer 32

Minimum urine production ~500 mL /day (20-30 ml/h) Obligatory urine volume needed to excrete waste solutes – typically ~600 mOsm / day. Owing to the limited ability of the kidney to concentrate urine to 1200mOsm/L. Maximum urine production ~ 20 000 mL /day (20 litres /day) Normal urine production ~1500ml /day = 1 mL /min Diurnal variation. Mechanisms of urine production allow rapid responses to changes in water intake / loss

Question 33

DIAGRAM OF ALL THE NEPHRON

Answer 33

DIAGRAM AND LECTURE CAPTURE | L1 S37

Question 34

countercurrent multiplier LoH

Answer 34

defined as - the formation of increasing osmotic gradient in the medullary interstitial fluid. Na+ and Cl- are concentrated in the medulla interstitial fluid as they are transported by symporters in the thick ascending limb of LoH and urea recycling. Osmosis is inhibited due the reduced permeability of the cells to water. The continued movement of fluid through the tubules means there is a constant build-up of ions = the formation of an osmotic gradient from 300 mOsml/L to 1200 mOsml/L

Question 35

loop of henle structure

Answer 35

Thin descending limb – permeable to water - no active reabsorption or secretion of solutes Thin ascending limb – impermeable to water - essentially no active reabsorption or secretion of solutes Thick ascending limb – impermeable to water - active reabsorption of sodium & other solutes

Question 36

Formation of dilute urine

Answer 36

Osmolarity of tubular fluid INCREASES as it flows down the descending limb LoH. Owing to increase in osmolarity of the surrounding interstitial tissue of renal medulla so fluid moves out of the tubule. Osmolarity of tubular fluid DECREASES as it flows up the ascending limb LoH. Owing to the removal of ions by Na+, K+ and Cl- symporters : and retention of water because the cells of the thick limb are impermeable to water. So solutes are leaving but water can not follow. Osmolarity of tubular fluid further DECREASES as it flows through DCT and CD. Some solutes are further removed and reabsorbed, in the absence of ADH the DCT and CD are impermeable to water so the tubular fluid is very dilute at this point = 65-70 mOsml/L.

Question 37

steps of formation of dilute urine

Answer 37

From ascending limb of loop of Henle the tubule is relatively impermeable to water. ∴ as pumps move solutes out of tubule lumen they leave behind a dilute tubular fluid when compared to plasma This leads to a dilute urine being excreted

Question 38

steps of formation of concentrated urine

Answer 38

The distal & collecting tubules / ducts are permeable to water in the presence of antidiuretic hormone (ADH) Water will move so that there is osmotic equilibrium with surrounding interstitium Note osmolarity of medullary interstitum ~1200mOsm/L/H2O This leads to a concentrated urine being excreted

Question 39

Counter-current exchange

Answer 39

Hairpin arrangement allows the nutrients to be delivered & water removed whilst minimising disruption to the medullary concentration gradient – counter current exchange Constant flow of urea and NaCl (lumen to interstitium and via vasa recta) - stops them precipitating in medulla MORE INFO IN L1 S44

Question 40

Renal regulation

Answer 40

Renal function is regulated by neural and hormonal influences. ``` Renal sympathetic nerves Renin-angiotensin-aldosterone system Antidiuretic Hormone (ADH) or Arginine vasopressin Atrial natriuretic peptide (ANP) Parathyroid hormone (PH) ```

Question 41

Renin- Angiotensin-Aldosterone system

Answer 41

When blood volume and BP is low walls of the afferent arteriole are less stretched and the juxtaglomerular cells secret RENIN (enzyme). Ultimately leads to Angiotensin II (potent vasoconstrictor) - Vasoconstriction of afferent and efferent arterioles – lower GFR - Increases reabsorption of Na+, Cl- and water by activating Na+/H+ antiporters. - Stimulate the adrenal cortex to release aldosterone – reabsorption of water increasing blood volume and BP.

Question 42

Renin –Angiotensin – Aldosterone - System

Answer 42

DIAGRAM AND LECTURE CAPTURE IN L1 S47

Question 43

Angiotensin Converting Enzyme

Answer 43

ACE – produced from both renal and lung epithelia ACE Inhibitors clinically very important. They are used as hypertension drugs, will stop systemic vasoconstriction They are commonly prescribed to stop impact of high BP ``` MAJOR TARGET FOR HYPERTENSION DRUGS benazepril (Lotensin) captopril (Capoten) enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril) moexipril (Univasc), and perindopril(Aceon), quinapril (Accupril), ramipril (Altace), trandolapril (Mavik) ```

Question 44

Diuretics and the control of Blood pressure

Answer 44

Diuretics are substances that promote the loss of Na+ and water. - Natural diuretics. - Osmotic diuretics. - Loop diuretics (Lasix, Frusemide) are the most powerful diuretics because they inhibit the formation of the medullar gradient. - Thiazide diuretics (Chlorithiazide, Diuril) acts on the DCT - reduces Na+ reabp. - Spironolactone is an aldosterone receptor antagonist. This is known as a K+ sparing diuretic. It acts because the K+ in the urine is from aldosterone-driven active tubular secretion into the late DCT and collecting ducts.