leanne (L1-2) Flashcards
Renal function and contribution to homeostasis
Blood ionic composition Blood pH Blood Volume Blood Pressure Blood osmolarity (concentration of solutes) Excretion of waste Hormone production Glucose levels
diseases from extreme body fluid volume
HYPOVOLAEMIA
too little body fluid vol
dehydrated
HYPERVOLAEMIA
too much body fluid vol
fluid overload
SYMPTOMS AND SIGNS L1 S6
define JVP and oedema
JVP - jugular venous pulse / pressure
Oedema - tissue swelling (peripheral, pulmonary, ankles etc)
Regulation of fluid balance
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.
define
- osmolarity
- osmotic pressure
- oncotic pressure
- hydrostatic pressure
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.
Tonicity and osmolarity
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)
if Pc > osmotic pressure
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
if Pc < osmotic pressure
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
STRUCTURE OF KIDNEY
DIAGRAM IN L1 S12
NEPHRON - FUNCTIONAL UNIT
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
JUXTAMEDULLARY NEPHRON
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
FUNCTIONAL OVERVIEW - STEPS THROUGH THE NEPHRON
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
bowman’s capsule structure
FUNCTIONS OF : mesangial cells / parietal layer / visceral layer
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
describe the feedbakc mechanisms of the bowman’s capsule
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)
glomerular filtration - what 3 characteristics allow the filtration?
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.
define filtration and which membranes/pressures allow it to happen
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.
NFP definition and equation
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
Three mechanisms control GFR:
- Renal Autoregulation a) Myogenic and b) Tubuloglomerular feedback
- Neuronal regulation
- Hormonal regulation
These work in two different ways:
- Adjustment of blood flow into and out of the glomerulus
- Alteration of glomerular capillary surface area
Renal autoregulation - MYOGENIC MECHANISM
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
Renal autoregulation - TUBULOGLOMERULAR FEEDBACK
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
role of juxtaglomerular apparatus
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
Substances filtered/reabsorbed and excreted
TABLE IN L1 S26
water reabsorption
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 :
- Insertion of water channels (aquaporins) - regulated by antidiuretic hormone (ADH)
- An osmotic gradient - generated by the countercurrent system in loop of Henle
- Glucose reabsorption in the PCT
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
- Reabsorption of sodium ions and secretion of hydrogen ions in PCT
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
- The distal part of the PCT is involved in passive reabsorption of certain ions and urea
A lot of passive diffusion down conc gradient
Cells are leaky - pericellular movement (between cells) and transcellular movement (through linked channels)
- Reabsorption in the Loop of Henle
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
- Reabsorption and secretion in the DCT and CD
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)
Control of ADH release
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)
ADH
where is it made? how is it transported? its 2 functions?
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
ADH mediated AQP2 export to the apical membrane
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)
urine production
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
DIAGRAM OF ALL THE NEPHRON
DIAGRAM AND LECTURE CAPTURE
L1 S37
countercurrent multiplier LoH
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
loop of henle structure
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
Formation of dilute urine
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.
steps of formation of dilute urine
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
steps of formation of concentrated urine
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
Counter-current exchange
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
Renal regulation
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)
Renin- Angiotensin-Aldosterone system
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.
Renin –Angiotensin – Aldosterone - System
DIAGRAM AND LECTURE CAPTURE IN L1 S47
Angiotensin Converting Enzyme
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)
Diuretics and the control of Blood pressure
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.
