Renal System Flashcards
What diseases is oral health associated with?
Cardiovascular disease Rheumatoid arthritis Respiratory disease Metabolic disease Kidney disease
Shared common risk factors for oral and systemic disease e.g. diet, socioeconomic status
In 2017, what percentage of all death globally were attributed to inflammation related disease
73.4%
What is the function of kidneys
1) Excretory organs
Process blood
Rid body of waste products of metabolism via urine
2) Maintain internal homeostasis of fluid
fluid + electrolytes
Gross anatomy of kidney
Two kidneys (produce urine) ->
Ureters (convey urine) ->
Bladder (store urine) ->
Urethra (void urine)
Common iliac artery -> Abdominal aorta -> renal artery
Common iliac vein -> inferior vena cava -> rena vein
top view
Back: spinous process of vertebra
kidneys in renal fat pad
in front: peritoneum and peritoneal cavity
Macroscopic kidney structure
3 sections:
1) Cortex
85% of kidney tubules/ nephrons
2) Medulla
Urine is concentrated
prevents excess water loss
3) Pelvis
Collection of urine -> ureter
(consult diagram for other structures)
Blood vessels of the kidney
Abdominal aorta-> (blood) -> renal artery -> kidney
Blood: 1.2L/min (1/5th of cardiac output)
What is the pathway of blood vessels of the kidney
Renal artery Segmental arteries lobar arteries Interlobar arteries Arcuate arteries Interlobular arteries Afferent arteries Glomercular capillaries Efferent arteries Peritubular capillaires (vasa recta) - Medulla Interlobular arteries
In the kidney where is the site of filtration?
Glomerular capillaries (glomerulus)
What is the basic functional unit of the kidney
The nephron
What does the nephron consist of?
Cortex:
Glomerulus
Bowman’s capsule
proximal convoluted tubule
Medulla:
Loop of Henle
Cortex:
Distal convoluted tubule
Collecting tubule
What are the types of nephron
Cortical nephron - short loop of henle
Juxtamedullary nephron - where urine is concentrated, reabsorbs water
What is the purpose of the nephron
- filter blood plasma
- excrete waste products of metabolism in urine
What occurs at the renal corpuscle ?
Filtration/removal
What does the renal corpuscle consist of?
Glomerulus
Bowman’s capsule
What does the renal tubule do?
Reabsorption and secretion (conservation/ fine tuning)
What does the renal tubule consist of?
Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Collecting duct
What is the structure of the glomerulus?
A network of fine capillaries
single layer of endothelial cells resting on a basement membrane
fenestrated - many pores
which allows rapid filtration of blood plasma
surrounded by bowman’s capsule
What is the structure of Bowman’s capsule
Cuplike structure surrounded by glomerulus
Bowman’s space = space within double layer:
Parietal (outer) layer
Visceral (inner) layer - comprised of specialised epithelium - podocytes - wrap around glomerular capillaries
What forms a filtration barrier in the kidney?
Glomerular endothelium
basement membrane
pedicels of podocytes
Pedicels share basement membrane with fenestrated endothelium
What does the filtration barrier do
Movement of filtrate through filtration membrane
freely permeable to water and small molecules
not permeable to large proteins or cells
charge of filtration slits determine which molecules are filtered -vely charged
What occurs in glomerular filtration
It is the first step in blood processing
1) unfiltered blood arrives at the glomerulus via the afferent arteriole
2) blood components filtered through the filtration barrier
3) Filtered blood exits the glomerulus via efferent artieriole
In the glomerular, how is filtration faciliated
By a pressure gradient
- glomerular hydrostatic pressure
- Afferent is wider then efferent
- blood arrives quicker then it leaves
In the glomerular filtration, what is filtered?
Water, glucose, AAs
Urea (protein waste), Creatine (muscle metabolism waste)
Electrolytes:
Na,Cl, Ca, K, PO, Bicarb
In glomerular filtration, what is not filtered?
Cells (RBC/WBC) Large proteins (Haemoglobin) Negatively charged protein (albumin)
What is the Glomerular Filtration Rate?
The rate at which blood is filtered through the glomerulus in to the Bowman’s capsule
Driven by glomerular hydrostatic pressure (+ capsular osmotic pressure)
counteracted by hydrostatic pressure in bowman’s capsule +
Glomerular osmotic pressure
GFR is influenced by hydrostatic and osmotic pressures. What else?
Systemic blood pressure
Renin-angiotensin system
Disease (inflammation - protein leaking across)
What is a health GFR
125ml/min
180l/day
How is kidney function to GFR
Kidney damage reduced GFR
reduced GFR = inefficent blood clearance and waste removal
Waste products accumulate in blood
How do you measure GFR
Serum creatinine (and urea)
What are the stages of chronic kidney disease
1 kidney damage - normal function GFR 90 -100 2 mild loss of function GFR 60 - 89 3a Mild to moderate loss GFR 45 - 59 3b Moderate to severe GFR 30 - 44 4 Severe - dialysis GFR 15 - 29 5 Failure - transplant - GFR 0 - 15
In the real corpuscle how much is filtered?
180l/day -> 99% reabsorbed
Discuss filtration from the proximal convoluted tubule
1) Primary Active transport:
Against concentration gradient
Na-K+ Pump = Basal-lateral side of cells
- requires ATP to change configuration ->ADP
1 ATP to move 3 X Na+ out of cell, in exchange for 2 x K+ into cell
- doesn’t need ATP to bring K+ back
- Drives Na against it’s concentration gradient
- facilitates 65 N+ reabsorbtion
2) Secondary Active transport Against concentration gradient Across apical surface Na Co-transporter Transporting glucose + amino acid Against concentration gradient
3) Passive diffusion
From high concentration to low concentration
Water
Follows Na+
via Aquaporin (due to hydrophobic phosoplipid bilayer)
Osmosis
4) Electrical gradient -
High concentration -> low concentration
Cl- and -ve ions follow Na+
What is not reabsorbed in the the proximal convoluted tubule
Creatinine
50% of Urea
What would occur, in the kidney, if only passive diffusion was used?
50% of filtrate would remain in the tubule to be excreted
50% of filtrate would be reabsorbed into the blood
How much does the proximal convoluted tubule reabsorbs?
2/3 of filtrate
Describe the concentration gradients in the PCT and Peritubular capillary for Na+
PCT tubule lumen - High
PCT tubule wall - Low
Interstitial space - High
Peritubular capillary - Low
Describe the concentration gradients in the PCT and Peritubular capillary for Na+
PCT tubule lumen - lower
PCT tubule wall - highest
Interstitial space - lower
Peritubular capillary - lowest
What are the reabsorption rates in the PCT?
Na active transport faciliates:
100% nutrient reabsorption - glucose/ amino acids “hitch a ride”
65% Water reabsorption - water follows Na+
65% negative ions follow electrical gradient
no effect on waste removal
- urea - 50% rebasorbed by passive diffusion
-Creatinine - no reabsorption
After PCT, how much filtrate continues through to the Loop of Henle?
60l (started at 180l)
What does sodium handling do in respect to tubular function?
Sodium transport used for reabsorption : reabsorption of nutrients, water, ions 65% reabsorbed in PCT 25% reabsorbed in ascending loop of henle up to 8% reabsorbed in DCT - depending
98% Na+ reabsorbed - 80% energy consumption used by kidney
Histology of proximal convoluted tubule
Simple cuboidal with microvilli brush border
increases surface area
Histology of distal convoluted tubule
Few/no microvilli
Histology of peritubular capillary
simple endothelium
Name the sections of the Loop of Henle
Thin descending limb
Thin ascending limb
Thick ascending limb
What properties does the thin descending limb have?
Contains aquaporin
freely permeable to water
What properties does the thick ascending limb contain
The site of active sodium reabsorption via Na/K pump on basal lateral side (????)
Sodium reabsorption via NKCC2 on apical membrane
What properties does the thick and thin ascending limbs have
No not contain aquaporins
imperable to water
How does the counter current multiplication work in the Loop of Henle/Medulla
Thick ascending limb = site of active sodium reabsorption
interstitium of medulla = salt
Water entering Loop of Henle flows of of tubule via osmosis
The concentration of filtrate as it descends the thin ascending limb increases (300->1200)
The concentration of filtrate as it ascends the thick ascending limb decreases (1200->100)
Counter current multiplication - water is pulled out of filtrate
In counter current multiplication, why does the concentration not equalise?
Vasa Recta
Maintains concentration gradient of medulla
-> structure
What does the Loop of Henle do?
Employs counter current multiplication to reabsorb water and concentrate urine
Na - actively reabsorbed from thick ascending limb
Creates and maintains high osmotic pressure within the medulla
water reabsorbed from thin descending limb
Vasa recta supports conc. grad. in medulla
What occurs at the distal convoluted tubule?
Fine tuning
site of fluid volume and electrolyte regulation
What hormone influence activity in the distal convoluted tubule and what do they do?
Na and water regulation
ADH - increase water reabsorption
Aldosterone - increase Na+ reabsorption
Atrial Natriuretic hormone - Promotes Na secretion
ADH + Aldosterone work together
Describe what happens in the DCT
Fluid that enters DCT is hypotonic with interstitium (less conc 100 vs 300)
in absence of external hormonal regulation a large volume of urine is produced
ADH, aldosterone, ANH acts on distal and collecting tubules
ADH:
inserts aquaporin
allows water to be reabsorbed from filtrate
small vol. con. urine produced
AVPR2 (vasopressin receptor 2) on basal lateral membrane on epithelium on DCT
Alderstone (steroid, can pass through membrane to nucleus):
upregulates activity and insertion of Na+K+ pumps and channels
small vol con. urine produced
ANH
inhibits action of ADH and aldosterone
removes aqua porin and sodium pump
large volume dilute urine produced
180 litres are filtered per day, how much is excreted?
1-2%
How does the change in blood pressure related to release of hormones in the DCT
Fall in BP ADH insert aquaporin Aldosterone insert sodium channels fluid reabsorption small volume con. urine raise in blood pressure
Rise in BP ANP inhibits ADH + Aldosterone fluid excretion large volume dilute urine lower blood pressure
What factors are GFR influenced by?
G hydrostatic pressure BC hydrostatic pressure G Osmotic pressure Systemic blood pressure - determine rate/force of afferent filtration RAAS Disease
How do the kidneys measure systemic blood pressure?
They use GFR as a proxy
Discuss how the GFR effects systemic blood pressure
If GFR increases, fluid flows faster through the tubules, there is less time to reabsorb Na = higher Na conc in DCT
If GFR lower, flow is lower, more time to reabsorb, Na conc lower in DCT.
What is the equation for excretion from the kidney?
Excretion = (filtration - reabsorption) + secretion
Describe secretion in the nephron
GFR = 100% into PCT
PCT
na + water = 65% reabsorpted
glucose + aa = 100%
Urea = 50%
Look of henle
Na (+K + Cl) = 25%
DCT
water = < 8%
GFR = 1% leaving collecting ducts
What the is Juxta-glomerular apparatus?
Connects the distal convoluted tubule with the glomerulus (afferent)
What does the juxta-glomerular apparatus measure and do?
Measures and responses to changes in Na+ conc of the filtrate - as a proxy for blood volume/pressure
What are the sections of the juxta-glomerular apparatus?
1) Macula densa
Epith cells near/on DCT
detect Na+ conc
in filtrate as flows through
2) Juxtaglomerular cells - modified smooth muscle
Adjust diameter of the afferent arteriole
vasodilate/constrict
talk directly to macula densa
3) Mesangial cells
supporting cells
extra and intra cells
How is homeostatic blood pressure maintained?
glomerular hydrostatic pressure maintained via:
Blood pressure drives
Glomerular hydrostatic pressure which determines
GFR which determines
Na+ conc of filtrate as enters DCT (which is in homeostatic limits)
this is detected by: Macula densa
No further signal to juxtaglomerular cells
in homeostasis: JGcell = large diameter of afferent arteriole maintained (compared to efferent)
What happens when blood pressure increases?
Tubuloglomerular Feedback
1) increased blood pressure drives
increase Glomerular hydrostatic pressure which drives
increased GFR causing
increase Na+ cons of filtrate entering DCT
Na flows out to Macula densa + water follows
Macula densa expands and swells + releases adenosine
Adenosine signals to Juxtaglomerular cells
Causes constriction of afferent arteriole
This protects glomerular capillaries from fluctuation in BP
glomerular hydrostatic pressure decrease
The knock on effect is:
decreased GFR
Na+ filtrate decreases
Macula densa detects and stops signal to JG cell
diameter of JG cells = normal (large diameter of afferent arteriol maintained)
Glomerular hydrostatic return to homeostasis.
2) Decreased blood pressure causes
decreased glomerular hydrostatic pressure
decreased GFR
less Na+ concentrate in filtrate going in to DCT
Na+ flows out of cell, water follows, cells shrivel
Macula densa releases prostaglandin
Tells Juxtaglomerular cells to vasodilate - but they are already vasodilated
Renin is secreted in response - activates RAAS system
Where does tubuloglomerular feedback occur?
High blood pressure:
Local to the kidney
no effect to systemic elevated blood pressure
function: to protect glomerular capillaries from fluctuations in kidneys
Low blood pressure:
activates RAAS
What does tubuloglomerular feedback regulate?
systemic blood pressure
Discuss RAAS
Renin angiotensinogen-system restores blood pressure via angiotensin II
It restores blood volume via increased fluid and salt retention.
1) Angiotensin produced in liver constantly + always present. Released into circulation
2) Low Na+ causes release of renin. Renin cleaves angiotensinogen into angiotensin I
3) Angiotensin converting enzyme produced in vascular endothelium of lungs - converts angiotensin iI into Angiotensin II. Angiotensin II = vascoconstrictor. Binds to receptors in arterioles. Increases blood pressure
short term measure
How is blood volume restores
RAAS:
restores blood volume via increased fluid and salt retention
Where does Angiotensin II target receptors and what do they do?
1) Arterioles - constriction
2) Hypothalamus - thirst (take on more fluid)
3) Pituitary Gland - release of ADH (epithelium in DCT = aquaporins = water reabsorbed)
4) Adrenal Medulla - release of aldosterone (DCT insert Na+ - Na+ reabsorb = more water in association with ADH)
restores blood and volume via increased fluid and salt retention
What are the consequences of chronic kidney disease?
Inadequate removal of fluid and waste products of metabolism
Inappropriate activation of RAAS (increase fluid and water retention)
what are the links between CKD and CVD
Diabetes
Hypertension
What are the causes of CKD
Hypertension diabetes High cholesterol kidney infections glomerulonephritis - oral bacteria polycystic kidney disease - hereditary kidney stones - waste crystals, blocks kidney long term use of NSAIDs - ibuprofen
What are the systems of CKD
hypertension nausea oedema - ankles, hands, feet, lungs blood/protein in urine anaemia weak/painful bones
How do you regulate hypertension?
Diet (reduce salt)/ weight loss
combination of anti hypertensive treatments
diuretics (furosemide)
ACE inhibitors/angiotensin receptor blockers (ARBS)
Aldosterone agonists (nuclear receptors or Na channels)
What does Furosemide target?
NKCC2
Na reabsorption is via NKCC2 on apical membrane
what is kidney failure?
Stage 5
end stage renal disease
less then 15% kidney function
dialysis and/or kidney transplant required
What is dialysis?
Artificial removal of waste, solutes, water and toxins from blood
two types
- Haemodialysis
- Periotoneal dialysis
How does ANP counteract RAAS?
RAAS increases BP
Baroreceptors detect rise in BP
Atrial Natriuretic peptide, released by epithelium cells in atria.
this inhibits effect of ADH, Aldosterone and Renin in RAAS
causes excretion of excess fluid
causes BP to return to homeostatic levels.
Juxtaglomerular detects and responds to changes in Na+ concentrate in filtrate. Give a summary
1) High Na+ -> adenosine -> vasoconstriction -> tubuloglomerular feedback
2) Low Na+ -> Prostaglandins -> renin -> RAAS
- > high BP via antiotensin II
- > high blood volume via aldosterone and ADH
3) ANP counteracts Aldosterone, ADH, Renin to remove excess fluid and lower BP
