Flashcards in Wall-1 Deck (82):
What is the major role of the kidney, how does it pull this off ?
maintaining total body contents at a stable and normal level, even in the face of changes in dietary intake or endogenous production rate.
The kidney, by changing its rate of excretion, will keep total body content at a normal stable level.
What is the role of NA ?
key solute in renal physiology. Na+ is restricted to extracellular space
total body sodium content determines size of extracellular fluid volume (ECFV) which determines BP/blood volume.
What happens when NA is increased ?
Increases total body Na+ content increase osmolality stimulates thirst increase water intake and stimulate vasopressin secretion tells kidney to conserve water.
What does CL do ?
in extracellular space Na+ is the primary cation and the anion is predominantly Cl-.
The total body content of Cl- is kept normal by the kidney
The other major anion is bicarbonate.
What does K do ?
Major Intracellular cation
What does BICARBONATE do ?
Major ECFV buffer
key factor in acid-base balance
kidney is involved in regulating plasma bicarbonate at a normal level which assists in keeping ph at a normal level (normal pH 7.40 )
What are the minerals the kidney is responsible for maintaining ?
calcium, phosphorus, magnesium
What are the waste products the kidney gets rid of ?
Kidney eliminates Waste material: urea (byproduct of protein metabolism), creatinine (byproduct of muscle metabolism), uric acid (formed from breakdown of nucleic acids)
Where is erythropoietin from ?
kidney is virtually the only source of erythropoietin.
glycoprotein produced in the kidney that stimulates the bone marrow to increase red blood cell production (increased reticulocytes).
What happens to the reticulocyte count when the kidney is not working ?
Less functioning kidney mass less erythropoietin production low reticulocyte count with a normocytic normochromic anemia.
Where is 1,25 (OH)2D3 made ?
1-alpha hydroxylase to produce 1,25 (OH)2D3
Kidney is virtually only source of the enzyme
final enzymatic step to produce 1,25 (OH) 2D3 or calcitriol which is the active form of Vitamin D.
Less nephron function Less of this enzyme Less of active metabolite of Vitamin D)
Where is renin produced ? What does Renin do ?
Kidney is only source of renin
produced at the juxtaglomerular apparatus by specialized cells in the afferent arteriole
catalytic enzyme that starts off the angiotensin-aldosterone cascade.
What are the paracrine and autocrine functions of the kidney ?
Production of bradykinin, prostaglandin, and endothelial factors ( NO and endothelia)
What does prostaglandin do in the kidney ?
production is critical in autoregulation of glomerular filtration rate (GFR)
particularly the vasodilatory prostaglandins such as PGI2, PGE2
What are the endothelial factors produced by the kidney and what is their role ?
nitric oxide (vasodilator)
most commonly produced when there is an endothelial injury
Very potent vasoconstrictor.
How does the kidney regulate blood pressure ?
1. homeostasis of sodium and water, maintaining normal extracellular fluid volume
2 control of the renin – angiotensin – aldosterone axis.
3. Production of circulating vasodilatory substances, predominantly from the renal medulla
How does renin affect blood pressure ?
Kidney is only supply of renin.
control of the renin – angiotensin – aldosterone axis. Angiotensin II is potent vasoconstrictor and aldosterone promotes Na reabsorption
The whole cascade is started in kidney by production of renin.
How does the kidney determine ECFV ?
Because ECFV is a function of total body sodium content and the kidney dictates the size of the extracellular space as well as total body water.
In addition to Blood Pressure what are some of the other functions of the kidney ?
1. Catabolism of small peptides such as insulin
2. Gluconeogenesis during fasting
3. Elimination of medications.
What is neutral balance ?
state in which dietary intake plus endogenous production exactly matches excretion rate of the kidney.
total body contents of the substance remains stable
What is positive balance ?
intake plus endogenous production > renal excretion rate (kidney output)
leads to increased total body content
What is negative balance ?
intake plus endogenous production < renal excretion rate
leads to decreased total body content
How can you determine if the kidney is not working ? An example is provided
In any clinical setting, to know if kidney is working properly, examine the urine contents.
Example: Clinical setting - Patient by clinical examination looks like he has too much Na+ content in his body (ECFV expansion). The kidney should be eliminating Na+. So, measure Na+ in urine to determine if kidney is working properly (i.e. excreting sodium to eliminate the excess body content).
What is the glomerulus ?
A capillary system from which an ultra filtrate of plasma enters into Bowmans space. It is made of fenestrated epithelium and basement membrane which prevent filtration of blood cells, proteins, and macromolecules.
What are Podocytes ?
The visceral epithelium that surrounds the glomeruli and contribute to the filtration barrier. It is a single layer thick
What is filtration in the glomerulous based on ?
Size and charge. The podocytes and basement membrane are negatively charged so most proteins ( also negatively charged) will not normally be filtered.
What is the normal blood flow to the kidneys ?
10 % of cardiac output.
What is the best index of overall kidney function ?
Glomerular filtration rate.
What are the 4 braod aspects of renal function ?
1. Gomerular Filtration
What is Glomerular Filtration ?
Deposit into Bowman’s space in the glomerulus,
Cell free protein free ultrafiltrate of plasma,
Blood/plasma entering glomerular capillaries. Filtrate formation is driven by Starling forces at the glomerular capillaries
What is reabsorption ?
Transport of water and certain solutes from tubular fluid through the peritubular capillaries into the bloodstream
What is secretion ?
Addition of certain solutes (but not of water) to the fluid in the tubules from the peritubular capillaries.
Example: Potassium, removal of daily intake of potassium occurs mainly through a tubular secretory process.
What is excretion ?
removal from the body of water and solutes as urine
--> Once urine is formed, it exits at renal papillae of the medulla and goes through a number of minor calyces that come together in 3-5 major calyces.
Then, coalesce into the renal pelvis.
What are the three sites of potential obstruction in the nephron ?
Three sites of potential obstruction within the ureter (as with kidney stone). Pelvic ureteral junction, crossover of pelvic brim and urinary trigone (bladder). Bladder functioning as a storage until voluntary voiding
What is unique about the male urethra ?
Male urethra goes through the median lobe of the prostate. It is longer and less UTI but every male’s prostate enlarges with aging (benign prostatic hypertrophy). The most common spot for obstruction in males is prostatic urethra (obstructive uropathy).
What is unique about the femail urethra ?
Female urethra is shorter, increase susceptibility to urinary tract infection (UTI) and cystitis. G(-) bacteria that ascend urethra into the urinary bladder.
What are the two types of nephrons ?
Cortical and Juxtamedullary
What is unique about the cortical nephrons ?
never operating at 100% capacity (important!): Ex. if we eat protein meal, our GFR goes up 20%. That is through reserve capacity of the cortical nephrons. When I donate kidney, I do not drop from 100% to 50%. I will be about 75% GFR because of reserve capacity within the cortical nephrons.
What size and functional aspects are unique to the Cortical nephrons ?
Cortical nephrons (closer to renal capsule, superficial nephron)
85% of total nephrons
Smaller than juxtamedullay nephron
Further from aorta arterial perfusion pressure is a little bit lower than juxtamedullary nephrons
Pressure inside the glomerular capillaries is a little bit lower than juxtamedullary nephrons filtration rate is lower
short loop of Henle (short loop nephrons)
What is unique to Juxtamedullary nephrons ?
15% of total number of nephrons, closer to corticomedullary junction, larger than cortical nephrons
Perfuse slightly higher pressure glomerular capillary pressure is higher filtration rate is higher
Longer loops of Henle
Some will descend to the renal papilla
critical part of urinary concentrating mechanism
If you had to pick one unique facto about the Juxtamedullary nephrons what would it be ?
--critical part of urinary concentrating mechanism--
maximal water conservation making maximally concentrated urine is critically linked to these juxtamedullary long loop of Henle nephrons
Medullary thick ascending limb is a major site of Na+ transport. Important for maximal Na+ conservation and for producing the hypertonic medullary interstitium.
efferent arterioles becomes descending vase recta, which is the only arterial blood supply to the medulla.
What is the blood distribution between the cortex and the medulla ?
90% of blood goes to cortex, while 10% goes to medulla. It is quite useful because medulla is hypertonic and if we send large amount of blood to the medulla, it will wash out the medullary solute and we cannot make concentrated urine. Urine can be no more concentrated than the medullary interstitium, as water moves via concentration gradients and is never actively transported.
What is the relation between the vasa recta and the loop of henle
The vasa recta follow the loops of Henle and have countercurrent arrangement.
What are 3 important aspects of the interaction between the vasa recta and the loop of henle ?
1.There can be solute transferred between ascending and descending vasa recta. Important in maintaining medulla in hypertonic fashion.
2.Oxygen transferred between ascending and descending vasa recta
When it descends medulla toward the tip of papillas, the O2 tension decline and leaves the medulla more susceptible to ischemia because it is getting progressively more hypoxemic.
3.In the peritubular capillaries, efferent arterioles from cortical nephrons become peritubular capillaries that surround the proximal convoluted tubule and all of the other tubular structures in the cortex. All the capillary network in the medulla comes from the vasa recta.
Are the Juxtamedullary Nephrons operating at 100% ?
uxtamedullary nephrons are always operating at full capacity placing them at increased risk from hemodynamic stress.
What is the Glomerulus ?
an invagination of capillaries surrounded by the fibrous Bowman's capsule, which is lined by parietal epithelial cells. In between the capsule and the capillaries is the urinary space which becomes contiguous with the beginning of the proximal tubule.
What is the Pre-Glomerular Resistance Vessel ?
What is the GBM composed of ?
endothelial cell, GBM, composed of type 4 collagen, Foot processes/slit diaphragms from the podocytes(visceral epithelial cells)
What are the capillary walls made of ?
Endothelial cells, glomerular basement membrane, delicate foot processes from the visceral epithelial cells
What is the difference between normal capillaries and Glomerular capillaries ?
1. designed to keep large proteins and cells inside the capillary
2. designed to keep albumin, the most abundant serum protein, in the plasma (where it belongs) and out of urinary space
3. perfumed by slightly higher pressures than normal capillaries: hydrostatic pressure is in favor of filtration
Highly permeable partly because endothelial cells have large fenestrae for filtration.
4. Foot process are very negatively charged.
What implications does the negative charge of the foot processes have ?
Albumin, a major serum protein is polyvalent anion (multiple negative charges).
Albumin is small enough to pass through the glomerulal capillary wall. But because components of the capillary wall are negatively charged, it’s repelled and maintained in the vascular space.
Foot processes from the visceral epithelial cells (podocytes) line up and surround every glomerular capillary.
What is the mesangium ?
provides the skeletal structure to support the capillary loops
Ground material holding glomerular capillary loops in the proper position.
Composed of mesangial cells and matrix material
Mesangial cells produce mesangial matrix
What is the function of the mesangium ?
contractile: contain actin and myosin (can alter capillary surface area available for filtration)
have macrophage function: ingest and remove circulating immune complexes.
Notice that Part of capillary loop abuts the mesangium No basement membrane across this area.
Does the mesangium function in the immune system ?
The mesangium is just removed from the circulation by the endothelial cell which has large fenestra. This is the way mesangial cells have access to the circulating immune complexes and can function as macrophage.
What are podocytes ?
(visceral epithelial cells)
arranged along the basement membrane.
at the slit diaphragm (negatively charged) between each foot process – major place where albumin is restricted from getting into the urinary space.
What are podocytes key to ?
Podocytes are the key cells in the proteinuric condition
Mutation in defective podocin or nephrin congenital nephrotic syndrome. Other podocyte protein mutations associated with familial focal segmental glomerular sclerosis, FSGS)
What is almost every Kidney disease with proteinurea associated with ?
Almost every kidney disease that is associated with heavy proteinuria has either acquired or congenital problem structure of visceral epithelial cells.
What makes up the Juxtaglomerular apparatus ?
(afferent and efferent arteriole and the macula densa )
What is the macula densa segment responsible for ?
Macula densa segment sense delivery how much tubular fluid is reaching macula densa (located at the end of the cortical thick ascending limb of Henle ).
What are all the structures in the nephron prior to the macula densa designed for ?
Everything prior to the macula densa (all tubular segments) are built for bulk reabsorption
**178L reabsorbed and 90% of it reabsorbed before reaching macula densa (located at the end of the cortical thick ascending limb of the loop of Henle)
**Distal nephron segments (after macula densa) are built for fine tuning
What is tubular Glomerular feedback ?
anatomical way each nephron to monitor delivery of filtrate to the distal nephron
each tubule feeding back to its glomerulus
What forces promote filtration out of the capillary ?
hydrostatic pressure within capillary
oncotic pressure within interstitium
What are the forces that oppose filtration out of the capillary ?
oncotic pressure within capillary
hydrostatic pressure within interstitium
What is the formula for Glomerular Filtrate Formation ?
GFR = LpS (ΔP - Δtau)
Lp = capillary wall permeability
S = glomerular capillary surface area available for filtration
ΔP= hydrostatic pressure gradient between capillary and Bowmans space
Δtau = oncotic pressure gradient between capillary and Bowmans space
What determines net flow in the capillary ?
Determined by the algebraic sum of the Starling forces, and by the filtration coefficient, Kf (based on how permeable the capillary is)
Glomerular capillaries – the most permeable, perfused at higher pressures than any other systemic capillaries. Have enormous surface area.
What is the hydrostatic pressure in Bowmans Capsule ?
Hydrostatic pressure in Bowman’s space is kept very low. When make filtrate, the tubule starts reabsorbing it. So, tubular pressure remains very low.
ΔP is always high throughout the length of the glomerular capillary.
What is the main factor that determines GFR ?
Main thing that will determine GFR is high glomerular capillary pressure
GFR is made by keeping pressure in glomerular capillary high and normal
Oncotic pressure inside Bowmans space is kept very low because albumin was prevented from entering the urinary space.
How is Glomerular Capillary Pressure regulated ?
Resistance vessels before and after glomerular capillary.
change resistance in either arterioles will affect pressure in glomerular capillaries
What happens if resistance is dropped in the afferent arteriole ?
if resistance is dropped in the afferent arteriole, plasma flow to the glomerular capillaries increases and there is greater transmission of the arterial pressure to the glomerular capillaries. The change in glomerular capillary pressure result in increased glomerular filtration rate
What happens if you constrict the Afferent arteriole ?
If constrict afferent arteriole (more resistance means less renal flow), less pressure in the glomerular capillary and thus less GFR.
What happens if you vasodilate / Vasoconstrict the efferent arteriole ?
Vasodilation of efferent arteriole (less resistance) more renal blood flow in the efferent arteriole drop in GFR due to lower glomerular capillary pressure
Vasoconstriction of efferent arteriole (more resistance) less renal blood flow in the efferent arteriole raise GFR by increasing glomerular capillary pressure.
How is GFR kept constant even when renal perfusion pressure changes ?
Autoregulating by change the resistance of arterioles
How will the autoregulation respond to hypoovolemia ?
Lower BP associated with mild to moderate hypovolemia, GFR kept constant over a very wide range of pressures through the autoregulatory response
Vasodilate afferent arteriole and/or constrict efferent arteriole to keep the capillary pressure high maintain GFR even though lower cardiac output and arterial pressure.
Is Urin flow autoregulated ?
Urine flow rate / volume is not autoregulated
Urine volume is not a good index of kidney function
Increased perfusion pressure results in increased urinary flow rate (pressure natriuresis): when more Na+ excreted , more water excreted; but that does not mean GFR changed
What is filtered load ?
Filtered load (mg/min) = (Px) x GFR, where Px is the plasma concentration of the substance
Filtered load represents the amount of substance in plasma that is filtered at the glomerulus per unit of time, how much filtered across capillary wall
What is excretion rate ?
Excretion rate (mg/min) = (Ux) x UFR, where Ux is the urine concentration of the substance and UFR is urine flow rate. [Dr. Wall often abbreviates UFR as V] UFR is not autoregulated.
What does excretion rate tell you ?
Excretion rate represents the amount of the substance excreted into the urine per unit of time
Urine flow rate is not autoregulated
Increased perfusion pressure results in increased urinary flow rate (pressure natriuresis)
Urine flow rate is not a good index of overall kidney function
GFR is the best index of overall kidney function
What are the properties of a good GFR marker ?
Present in plasma at a constant concentration, not protein bound in plasma
Freely filtered at the glomerulus
Once filtered, no reabsorption, secretion, synthesis, or metabolism occurs totally excreted ( filtered load equals excretion rate)
What is renal clearance ?
represents the volume of plasma cleared of the substance (e.g. creatinine) via elimination into the urine per unit of time
Units = ml/min
Renal clearance = (Ux x UFR)/Px (ml/min)
How would you define renal clearance ?
The renal clearance (ml/min) of any substance cleared by the kidney can be defined as: (Clearance of substance x) = (urine concentration of x) x (urine flow rate)/plasma concentration of x
What are the clinical GFR markers ?
Exogenous example: inulin, radioisotope iothalamate (iv injection, cumbersome and expensive)
Endogenous example: creatinine (~10% secretion, so over-estimates GFR)
Creatinine clearance is the best clinical estimate of GFR and kidney function
Given these properties, the filtered load of inulin is equal to its excretion rate