Renal Flashcards
What are the functions of the kidneys?
- Regulation of water, inorganic ion balance and acid-base balance
- Removal of metabolic waste products from blood (excretion in the urine)
- Removal of foreign chemicals from the blood (excretion in the urine)
4.Production of hormone/enzymes
Which 3 major hormones/enzymes are produced by the kidneys?
- Erythropoietin : hromone controlling erythrocyte production
- Renin: enzyme controlling formation of angiotensin + influences blood pressure + Na+ balance
- 1,25-dihydroxyvitamin D: active vitamin that influences calcium balance
What is the weight of the kidneys?
Where are they?
150 gram/kidney (everyone has a pair, not variation of weight)
Placed behind the peritoneum on each side of vertebral column against posterior abdominal wall
(bottom of the back)
Under the diaphragm, connected to the bladder
What are the different parts of the kidneys?
Renal cortex (outside layer)
Renal medulla (inside the cortex)
Renal pelvis (part in the middle) –> poors into the ureter
Renal Artery and Renal veins supply blood to the kidneys separate into interlobar artery –> arcuate artery –> interlobular artery
Filtration unit of the kidney = Nephron which is supplied by interlobular artery
What are Nephrons?
How many are there in each kidney?
Each kidney has 1 million subunit
Each Nephron has:
Renal corpuscle –> Glomerulus (capillary loops) and Bowman’s capsule
Tubule
What is the renal corpuscule composed of?
Afferent arterioles (Glomerulus) + Bowman’s capsule (surrounded by layer of epithelial cells)
Around the Glomerulus, Bowman’s capsule visceral layer (podocytes) directly on the glomerulus, inside of the bag, Bowman’s space, on the outisde –> Bowman’s capsule’s parietal layer
What does the Glomerular capillary wall look like?
REVIEW SLIDES 17-21
What are the 3 processes of urine formation?
- Glomerular filtration (blood filtered by gloumerulosa, no urine made)
- Tubular secretion
- Tubular reabsorption
What consists in the Glomerular filtration phase of urine formation?
Filtration of plasma from the glomerular capillaries in to the bowman’s space
Glomerular filtrate = fluid in Bowman’s space, is cell-free + contains all substances from plasma except for proteins (about same concentrations)
fluid goes from Glomerular capillary (afferent arteriole) to the Bowman’s space
What consists in the Tubular secretion/reabsorption phase of urine formation?
Reabsorption: Tubules –> Peritubular capillaries
Secretion: Peritubular capillaries –> tubules
*peritubular capillary is a efferent arteriole
What determines the amount of a substance excreted in urine?
Amount excreted = amount filtered (in glomerular filtration) + amount secreted - amount reabsorbed
What is the difference between PAH (para-amino-hippurate), sodium, water and glucose in the formation of urine?
PAH : a little bit filtrated, none reabsorbed, the rest secreted (none in the blood left)
Na+ and water: a bit filtrated, almost all reabsorbed, non secreted (a little bit in urine)
Gluose: a little bit filtrated, all reabsorbed, none secreted, none in urine except if diabeties
What is filtrated by glomerular filtration?
Plasma –> Filtrate
- Water
- Low-molecular weight
What is not filtrated:
Cells (RBC, lymphocytes, Leukocytes)
Proteins (albumin, globulins)
Protein bound subtsances (1/2 calcium ion, fatty acid)
Which forces are involved in filtration?
Glomerular capillary blood pressure (Filtration, goes from capillary to Bowman’s space) = 60 mmHg
Fluid pressure in Bowman’s space (opposing to filtration) = 15 mmHg
Osmotic force bc proteins in plasma (wants to keep liquid in to reduce osmotic pressure, opposing to plasma) = 29 mmHg
*osmotic pressure also called oncotic pressure
Net glomerular filtration pressure = P(GC) - P(BS) - osmotic pressure(GC) = 16 mmHg
What is the glomerular filtration rate?
GFR is regulated by:
- net filtration pressure
- membrane permeability (can get lower in pathological conditions)
- surface area available for filtration
Normal GFR (70kg person) = 180L/day (125mL/min)
N.B plasma volume of this person = 3.5L so plasma filtered 51%/day (180/3.5)
What mechanisms regulate GFR?
Deceased GFR:
Constriction before filtration site (afferent arteriole)
Dilatation of the efferent arteriole (after the site)
Increased GFR:
Constriction of the efferent arteriole (after filtration site)
Dilatation of the afferent arterioles
What determines the filtered load?
Filtered load = GFR * plasma concentration of the substance (g/day)
Filtered load > amount excreted: net absorption
Filtered load < amount excreted: net secretion
What is tubular reapsorption?
(General facts)
2 types: paracellular (directly from tubular lumen to peritubular capillaries) *accross tight junctions
transcellular (from tubular lumen through tubular epithelial cell, to peritubular capillaries)
Facts:
1. Filtered load are enormous, generally greater than amount of the substance in the body
- reabsorption of waste products in relatively incomplete (urea = 44% reabsorbed)
- reabsoprtion of most useful plans components is relatively complete (ex: water (99%), ionrganis ions, organic nutrients, Na+ (99.5%), glucose (100%))
- Reabsorption of some substances NOT regulated (ex: glucose, amino acids), some other are highly regulated (water, inorganic ions)
What are the 2 mechanisms of reabsorption?
Diffusion and Mediated transport
Reabsorption by diffusion often across tight junctions connecting the tubular epithelial cells
Reabsorption by mediated transport ONLY across tubular cells (trans cellular epithelial cells), requieres participation of transport proteins in plasma membrane of tubular cells
*Usullay coupled to reabsorption of Na+
What is transport maximum (Tm)?
Limit when membrane transport proteins become saturated, tubule can not reabsorb substance any more
ex: people with diabetes mellitus have such high concentration of glucose that filtered load of glucose»_space; capacity if the tubules to reabsorb glucose (Tm exceeded) so glucose in urin (glucosuria)
How does tubular secretion work?
Where does it happen?
Mediated by 2 mechanisms: diffusion and transcellular mediated transport
*Tubular secretion usually coupled with reabsorption of Na+
Most important substances secreted by tubules: H+ and K+
What are the different roles of different parts of tubules?
In proximal tubule: reabsorbs most filtered water and solutes + major site of secretion for various solutes (except K+)
Henle’s loop: reabsorbs relatively large qties of major ions (less water)
DCT/CD: volume of water and masses of solutes reaching here are relatively small. (Fine-tuning)
Determines the final amounts excreted in the urine by adjuting reabsorption (and secretion in few cases)
*HOMEOSTATIC controls here
What is clearance?
Clearance = volume of plasma from which that substance is completly removed by the kidney/unit time
Clearance of substance S (Cs) = Mass of S (excreted/time)/plasma concentration of S
Where mass of S excreted/time = Urine concentration of S (Us) * Urine volume/time (V)
Cs = Us*V/Ps
What is the importance of inulin in clearance measurement? (not insulin)
Inulin = polysaccharide administered intravenously, freely filtered at glomerulus, but NOT reabsorbed, NOT secreted or NOT metabolized by tubule
Cinulin = GFR
*most accurate marker of GFR
What is the importance of creatinine in clearance measurement?
Creatinine = waste product produced by muscle
Freely filtered at glomerulus and NOT reabsorbed
Secreted at the tubule but amount is very small
Not metabolized
GFR clinical marker (easier bc body produces it so no need to inject, just take a blood and urine test)
What are the different source of water intake and outputs of the body?
Intake:
- Liquids (1200 mL)
- Food (1000mL)
- Metabolically produced (350mL) (don’t count it, normally just subtract it to insensible loss)
Output:
- Insensible loss (skin and lungs) (900mL - metabolically produced = 500 mL)
- Sweat (50mL)
- Feces (100mL)
- Urine (1500mL) –> most important output
Total of 2550mL in and out/day
What are the different source of Sodium intake and outputs of the body?
Intake:
- Food (10.50g) –> varies drastically depending on diet (areas in the world)
Outputs:
- Sweat (0.25g)
- Feces (0.25g)
- Urine (predominant output on NaCl, depends on intake, the others don’t) (10.00g)
*We are in water and Na balance (output = intake)
Between what values can water and NaCl output varie in a day?
Water: 0.4L/day - 25L/day
NaCl: 0.05 g/day - 25 g/day
What happens with the filtration, secretion and reabsorption of water and Na? (general)
freely filtered, 99% reabsprobed, NO secretion
Majority of sodium and water reabsorption occur int the proximal tubule (2/3)
Major hormonal control of reabsorption occur in the DCT and CD
How do the general mechanisms of reabsorption of water and Na function?
Na reabsorption = ACTIVE process occuring in ALL tubular segments (except the descending thin limb of Henle’s loop)
Water reabsorption is by DIFFUSION and in dependent upon Na reabsorption
How (in details) does the Active sodium reabsorption occur?
On the basolateral membrane:
Active Na+/K+ - ATPase pumps transport sodium out of the cells and keep the intracellular concentration of sodium low
On the apical (luminal) membrane:
Sodium moves downhill from the tubular lumen –> the tubular epithelial cells (bc Na+ intracellular concentration is low)
Each tubular segment has different mechanisms
ex: proximal tubule have Na+-H+ antiporter and Na+-glucose cotransporter
In the CCD, diffusion via Na+ channels
What is sensing total body sodium?
Sodium in the major extracellular solute –> Changes in total body sodium –> changes in extracellular fluid volume (so we can use extracellular fluid volume sensors)
Total body water (60% of BW) –> extracellular fluid (20% of BW) –> 3/4 = interstitial fluid + 1/4 = plasma
(40% of BW is intracellular fluid)
Total body sodium is sensed as INTRAVASCULAR FILLING by baroreceptors in the cardiovascular system
Attention: plasma concentration of Na is NOT a marker for total body Na
PNa only reflects the relative relationship of total body Na and water
Which system is responsible for regulation of sodium in the body/ in the kidneys?
The reabsorption = major role
GFR = minor role
How does the GFR influence the renal regulation of sodium?
Example, what happens when diarrhea?
3 sets of baroreceptors to activate renal sympathetic nerves depending on volume of plasma (intravascular volume)
↑ Na+ and H2O loss due to diarrhea (so less of them) → ↓ in plasma volume → ↓venous pressure → ↓venous return → ↓atrial pressure → ↓ ventricular end-diastolic volume → ↓Stroke volume → ↓ Cardiac output → ↓ Arterial blood pressure
(or →↓ venous pressure → directly to)
↑ activity of renal sympathetic nerves → IN THE KIDNEYS: ↑ constriction of a.a. → ↓Net GF pressure → ↓GFR → ↓Na+ and H2O excreted
How is renal sodium regulated by reabsorption?
Key hormone: aldosterone (steroid hormone secreted by adrenal cortex, zona glomerulosa)
Aldosterone stimulates Na reabsorption in the DCT and CCD
No aldosterone → 2% of filtered load is excreted (35g of NaCl)
High aldosterone → 0% of filtered load is excreted
Where in the Kidneys does Na reabsorption occur?
In proximal tubule → 67%
In thick ascending limb → 25%
DT → 4%
Cortical collecting duct → 3% *Hormone control at the CCD
How does aldosterone affect different pumps of the Na reabsorption?
- Aldosterone increases H+ secretion
- Aldosterone increases all transport proteins → Na more reabsorbed
How does renin-angiotensin system work?
- Liver secretes angiotensin → blood
- Kindeys secrete renin → blood
- In the blood → angiotensin + renin → Angiotensin I
- In blood → angiotensin converting enzyme + angiotensin I → angiotensin II
- Angiotensin II → into adrenal cortex → secreted aldosterone
What is the Juxtaglomerular apparatus?
It is a structure responsible for renin secretion and ensures a proper gromerular flow
Contains gromerular afferent and efferent arterioles
Sympathetic nerves innervate the juxtaglomerular cells, 3 different stimulation sources:
- Tubules
- Afferent nerves
- Macula densa (sends signal to the tubular lumen)
How does regulation of renin secretion by extracellular fluid volme influence Na balance?
↓ Plasma volume : ↑ Activity of renal sympathetic nerves (3 baroreceptors), ↓ Arterial pressure (less stretch, afferent arterioles collapse), ↓ GFR → ↓ flow macula densa → ↓ NaCl delivery to macula densa (transmit signal to renin secreting cells)
All of that leads to Renal juxtaglomerular cells ↑ Renin secretion!!! → ↑ plasma renin → ↑ plasma angiotensin II → ↑ Aldosterone (in Adrenal Cortex) → ↑ Plasma aldosterone → ↑ Sodium reabsorption (in CCD) → ↓ Na excretion
*Aldosterone does NOT stimulate H2O reabsorption directly in the CCD
What are other factors than renin secretion that influence renal sodium excretion?
Atrial natriuretic peptide (ANP):
*opposit as tubular aldosterone, act when too much salt and atria expands
ANP = peptide hormone secreted by cells in the cardiac atria
Acts on the tubules to inhibit Na reabsorption and increase GFR
Increased total body Na (↑ extracellular fluid/plasma volume stimulates ANP secretion
Blood Pressure:
↑ blood pressure → ↑ Na excretion (pressure natriuresis) (can be pathological)
What is the process by which the ANP influences Na reabsorption?
*ANP = opposit than aldosterone
↑ Plasma volume → ↑ distension (in cardiac atria) → ↑ ANP secretion → ↑ plasma ANP → :
- ↓ plasma aldosterone
- ↓ Na+ reabsorption ( in tubules of the kidneys, in CCD?)
- afferent dilatation + efferent constriction → ↑ GFR
All of that increases Na excretion
What is a Hypoosmotic, Isoosmotic and Hyperosmotic solution?
Hypoosmotic: total solute concentration less than normal 300 mOsm (more water, less solute)
Isoosmotic : total solute concentration equal to that of normal extracellular fluid
Where is the majority of water reabsorption done in the kidneys?
Where is hormonal control?
2/3 → in the proximal tubule
Major hormonal controle of reabsorption in the CD
What does Water reabsorption mainly depend on ?
Depends on Na reabsorption in the proximal tubule (which affects osmolarities of tubular lumen and interstitial fluid)
*water reabsorption done by osmosis
- Na reabsorbed from tubular lumen → interstitial fluid across epithelial cells
- Local osmolarity of lumen ↓ as local osmolarity of intersitium ↑
- Difference in osmolarity causes net diffusion of water from lumen → interstitial fluid via tubula cell’s plasma membranes (tubular epithelial cells) and via tight junctions
- From interstitum, H2O, Na and everything else dissolved in interstitial fluid move together by bulk flow into peritubular capillaries
In tubular lumen, local osmolarity in low when Na is reabsorbed → H2O is reabsorbed by osmosis to make solutions in interstitial fluid (hyperosmotic) and in tubular lumen isosmotic
Where does dynamic regulation of water reabsorption takes place?
in the Collecting duct, 2 critical components:
1. high osmolarity of the medullary interstitium
2. Permeability of CD to water (regulated by vasopressin)
How does urine concentraiton function?
Countercurrent multiplier system:
- The kidney has ability to concentrate urine up to 1400 mOsm/L
- Urinary concentration → as tubular fluid flows through the medullary collecting duct (starts in the cortex but mainly in medullary CD)
- Urinary concentration depends on hyperosmolarity of the interstitial fluid. Vasopressin → water diffuses out of duct → interstitial fluid in the medulla to be carried away.
What does water permeability of the tubules depend on?
- Water reabsorption depends on the water permeability of the tubules
- Permeability of the epithalium depends on the tubular segment ex: proximal tubule = high permeability to H2O
- Permeability depends on presence of aquaporins in plasma membrane
- H2O permeability in CCD and MCD is subject to physiological control + vasopressin
Where is water reabsorbed in the kidneys?
Proximal tubule = 67%
Descending thin limb of Henle = 15% (freely permeable)
NOTHING in TAL (impermeable, NaCl reabsorption)
CCD and MCD → hormonal controle (vasopressin)
What is Vasopressin?
aka anti-diuretic hormone (ADH)
- Peptide hormone
- Produced by group of hypothalamic neurons
- released from posterior lobe of pituirary gland
Couples to GPCR V1 (smooth muscle) + V2 (kidney)
Stimulates insertion of aquaporins in the luminal membrane of CD cells and increase water permeability
When vasopressin → CD becomes permeable to water → reabsorption of water
when no present → impermeable → water diuresis
By what is diabetes insidious (DI) caused?
By malfunction of vasopressin system (vasopressin des NOT work) : mutation of V2 receptors in kidneys (don’t respond) or enzymes degrade of digest vasopressin
*usually in complaction of pregnancy
What is the role of vasopressin?
How is its secretion regulated?
Vasopressin regulates excretion of water by regulating its reabsorption rate from the tubules.
2 mechanisms regulate vasopressin secretion:
1. Osmoreceptor control (most important) - senses filling
2. Baroreceptor control (less sensitive)
How do osmoreceptors control vasopressin secretion?
*Opposit than osmoreceptors
Excess H2O ingested → ↓ Body fluid osmolarity (more H2O oncentration) → ↓ Firing by hypothalamic osmoreceptors →
In the posterior pituitary: ↓ Vasopressin secretion → ↓ Plasma vasopressin
In Collecting ducts: ↓ Tubular permeability to H2O → ↓ H2O reabsorption
→ ↑ H2O excretion
How do baroreceptors control vasopressin secretion?
*Opposit than osmoreceptors
↓ Plasma volume → ↓ Venous, atrial and arterial pressures → Reflexe mediated by cardiovascular baroreceptors →
In the posterior pituitary: ↑ Vasopressin secretion → ↑ Plasma vasopressin
In Collecting ducts: ↑ Tubular permeability to H2O → ↑ H2O reabsorption
→ ↓ H2O excretion
*Vasopressin stimulates keeping H2O in the body by making tubual reabsorption membrane more permeable to H2O
*Baroreceptors = safety net if plasma very low, not in tiny changes
What makes you feel thirsty?
Mostly ↑ Plasma osmolarity → osmoreceptors → increase thrist
Dry mouth, throat → increase thrist
↓ Plasma volume → Baroreceptors (but less sensitive) → increase thirst
Metering of water intake by IG tract (when drink, immediately stop being thirsty even though not absorbed)
What mechanism follows severe sweating?
Sever sweating → Loss of hypoosmotic salt solution (loss of H2O > loss of Na) → ↓ Plasma volume + ↑ Plasma osmolarity (decrease H2O concentration)
↓ Plasma volume → :
↓ GFR + ↑ Plasma aldosterone → ↓ Na excretion
↑ Plasma vasopressin → ↓ H2O excretion
