L7 Renal Flashcards
Acute kidney injury
sudden, temporary, but sometimes fatal loss of kidney function
Chronic Kidney Disease
any condition that decreases kidney function over a period of time
End-stage renal disease
total and permanent kidney failure
Two common risk factors for Chronic Renal Failure
Diabetes
Hypertension
Drugs to avoid with kidney disease
antibiotics
antidepressants
antivirals
chinese herbal medicines
cholesterol lowering statins
diuretics
NSAID pain relievers
Stomach-acid reducers
Consequences of renal failure
HTN
Metabolic Acidosis
Muscle Weakness
Osteoporosis
Anemia
CNS/PNS?autonomic dysfunction
Renal Failure and Osteopororsis
excreting calcium more, retaining phosphate
Renal Failure and ANemia
kidneys produce erthryopoetin, decreases with failure
Renal Failure and CNS, PNS, Autonomic Dysfunction
buildup of urea, increased BUN. Toxic to nerves
Plasma K+ level
3.7 to 5.1 mEq/L
both hypo and hyper are dangerous, especially for cardiac function
you should always review electrolyte panel
BP Control
Lifestyle modifications
Anti-hypertensive medications
Lifestyle Modifications (BP control)
DASH diet
exercise
no smoking
limited alcohol
Anti-hypertensive medications (BP control
ACE inhibitors
BBs
CCBs
Diuretics
vasodilators
Management of renal disease
BP control
Anemia Control
Dialysis
Renal transplantation
Hemodialysis
Cleaning the blood, specifically from nitrogenous waste (urea and creatanine) products, metabolites from drugs
prescribed at less than 15% of function left
Arteriovenous fistula for hemodialysis
Surgically created connection between an artery and a vein that makes needle placements for dialysis easier
Takes 6 weeks to heal
Can be used for years, allows blood to flow out/in w/out damaging veins
Precautions for arm with AV fistula
No BP
Keep the port clean
No heavy lifting
Do not sleep with arm under head
Peritoneal Dialysis
allows individuals to do their own dialysis
blood is cleaned w/out removing it from the body
Can exercise training help patients with CKD?
Adults w/CKD have VO2max that are 1/3 to 1/2 that of age-matched sedentary adults w/out kidney disease
Exercise can: improve BP control, increase functional capacity, increase H/H levels, improves glucose metabolism
Functions of the kidneys
- Regulate ECF volume through urine formation
- Regulate blood volume and BP
- Regulate concentration of electrolytes
- Regulate concentration of waste products in blood
- Regulate pH
- Secrete erythropoietin, production of RBCs
- Excrete metabolites
Kidney Medulla
-renal pyramids separated by renal columns
-pyramid contain minor calyces, which become major calyces, and then renal pelvis
Nephron
urinary tubules and associated blood vessels
Filtration
Blood to tubules
water and solutes that pass from the plasma to inside of glomerular capsule and tubules
Secretion
Blood to Tubules (active)
active transport of substances from plasma into tubules
opposite of reabsorption
Reabsorption
Tubules to blood
return of filtered water and molecules from tubules into plasma
Excretion
Fluid and solutes leave body in urine
Proximal Convoluted Tubule (Reabsorb)
65% of H2O, NaCL, K+ Reabsorbed
100% of AA and glucose reabsorbed
Loop of henle makeup
Thin descending limb
Thin ascending limb
Thick ascending limb
Loop of henle (reabsorb)
20% H2O, NaCL reabsorbed
Macula Densa
sense the glomerular filtration rate (GFR)
cells are in the ascending loop
Juxtaglomerular apparatus
macula densa and afferent arterioles
Hormones of collecting ducts
aldosterone
ADH/vasopressin
Descending Limb
Passive H2O reabsorption
water goes into the vasa recta
Ascending Limb
NaCL active reabsorption, goes into the interstitum
Reabsorption of H2O and NaCL
85% of it is not under hormonal control
Pathway after a nephron
Collecting duct > minor calyx > major calyx > renal pelvis > ureter > bladder > urethra
Cortical nephrons
urine formed here is about the same concentration as plasma
short loops of henle
Juxtamedullary nephrons
Critical to produce concentrated urine
long loops of henle
Osmosis
passive diffusion of water from hypotonic to hypertonic solution
Renal blood vessels
Afferent arteriole
Glomerulus
Efferent arteriole
Vasa Recta
Afferent arteriole
delivers blood into glomeruli
Glomerulus
capillary network produces filtrate that enters urinary tubules at glomerular capsule
Efferent arteriole
delivers blood from glomeruli to peritubular capillaries
Vasa recta
-straight arterioles and venules that lie parallel to the loop of henle
-blood flows through the tight turn at very slow rate
-Proximity of vasa recta to loop of henle AND the slow flow rate are critical to maintain the concentration gradient in renal medulla
Bowman’s capsule
surrounds glomerulus
where GLOMERULAR FILTRATION occurs
What does RBC in the urine indicate?
that there has been damage to the glomerular filtration membrane
What makes up the glomerular filtration membrane?
(PLASMA) Capillary endothelium
Basement membrane
Foot processes of podocyte of glomerular capsule
Endothelial cells of glomerular capillaries
have LARGE pores
permeable to plasma, H2O, solutes
pores do not allow formed elements of blood to pass through
Basement Membrane
Filtrate must pass through basement membrane
thin glycoprotein layer that is negatively charged, does not allow plasma proteins to pass through
Podocytes of visceral layer of Bowman’s capsule
spaces between foot pedicels from small filtration slits that allow filtered molecules to enter interior Bowmna’s capsule
Ultrafiltrate
fluid that enters the glomerular capsule
formed under the hydrostatic pressure of blood
Glomerular filtration rate
measures kidney function
volume of filtrate removed from the blood each minute
averages 180 L/day
decreases with age and w/kidney dysfunction and disease
How to estimate GFR
can be closely estimated by blood, creatinine
one of the best tests to measure kidney function
used to determine stage of kidney disease
Why does GFT need to be regulated?
needs to be high enough to eliminate wastes
shouldn’t be so high that it causes excessive BV loss
How is GFR regulated?
vasoconstriction or vasodilation of afferent arterioles affects the rate of blood flow to the glomerulus
Forces across glomerular capillaries
- Beginning net = +16 mmHg
- End net = 0 mmHg
Pressure going into bowman’s space stays the same, and the pressure going out from bowman’s space. But, the pressure of the glomerular capillary changes due to the amount of plasma proteins
What systems regulate GFR?
sympathetic nervous system
autoregulation of intrinsic to the kidneys
renin-angiotensin system
SNS activation of glomerulus
causes vasoconstriction of afferent arterioles
causes decreased glomerular capillary hydrostatic pressure AND decreased urine output
ultimately preserves blood volume to muscles and heart
Renal autoregulation
ability of kidneys to maintain a relatively constant GFR under widely changing BPs
allows GFR to remain constant, even with changing BP
How does autoregulation occur?
Different from SNS input
- Effects of locally produced chemicals on afferent arterioles
- Tubuloglomerular feedback from macula densa
What is reabsorbed and filtered?
glucose and AA, water
What is never filtered?
potassium
antibiotics
formed elements/plasma protein
Reabsorption details
180 L of ultrafiltrate are produced/day
only 1-2 L urine is excreted
most filtered solutes and H2O from the ultrafiltrate are returned back into the peritubular capillaries
Obligatory water loss
minimum of 400 ml/day urine is necessary to excrete metabolic wastes (urea and creatane)
this is what you need to survive
Nephron makeup
urinary tubule and associated blood vessels
Reabsorption in PCT
- 65% of salt and water that enter the glomerular capsule is reabsorbed across PCT and returned to the plasma
- Total solute concentration is same as plasma (isosmotic)
How is that fluid in PCT is 1/3 of original volume but it is still isosmotic with plasma?
Active Na+ transport and osmosis
What things are reabsorbed?
Na+
Cl-
H2O follows by osmosis
glucose
amino acids
65% of Na, Cl, H2O, and K+ is reabsorbed
100% of glucose and AA are reabsorbed
Proximal convoluted tubule
single layer of cuboidal cells
Na/K ATP located in sides of cell membrane creates GRADIENT of Na, causes diffusion into cell
Cl follows electrical gradient
H2O follows by osmosis
Glucose Reabsorption
100% occurs in PCT
filtered but not excreted (along with AAs)
Cotransporters help to reabsorb glucose and AA
What occurs in cotransporter saturation?
amount of cotransporters are limited
Glycosuria = glucose in urine
happens when glucose is >180 mg’dl
sign of diabetes
Osmolality and Tubules
the interstitial fluid surround teh tubules has to be hypertonic to pull water out of the tubules
How is the concentration gradient maintained in the kidneys?
countercurrent multiplier system
vasa recta
Countercurrent multiplier system
amount of salt determines how much H20 and Na leaves
refers to the interaction between the descending and ascending loop of henle
- More salt is added by PCT
- Higher osmolarity of ECF, the more water that leaves the descending limb
- The more water that leaves, the saltier the fluid in the tubule becomes (more urine is produced)
- The saltier the fluid in the ascending limb, the more salt the tubule pumps out
positive feedback loop
Role of Vasa Recta
pulls the water leaving the tubules into the blood to prevent dilution of the interstitial fluid
also allows NA to remain in the intersitial fluid of the medulla
Role of urea
nitrogenous waste product from protein
both ascending and terminal collecting duct are permeable to urea
recycyled through these two areas, contributing to the osmolality of the intersitial fluid in the inner medulla
Order of the nephron
Bowman’s capsule
PCT
Loop of henle
Macula densa
DCT
Collecting Duct
Order of chemical processes in nephron
Filtration
Reabsorption
Secretion
Excretion
Collecting ducts anatomy
receive fluid from DCTs of nephrons
pass through renal pyramid into minor calyx
Functions of collecting ducts
- Reabsorption–> h2o, influenced by ADH
- Secretion–> potassium, influenced by aldosterone
Dehydration and ADH
Dehydration causes ADH to be released
- Increased salt/increased plasma osmolality
- Triggers osmoreceptors/thirst
- release of ADH from posterior pituitary
Vasopression receptors
V1: vascular smooth muscle –> vasoconstriction
V2: cells of renal collecting duct –> water reabsorption
Diabetes Insipidus
deficiency of ADH/vasopression
Aldosterone
The final concentrations of Na and K are varied in DCT and collecting ducts because of aldosterone
Triggers: angiotensin 2, high plasma K, low plasma Na
increases blood pressure, reabsorbs Na and K secretion. results in water retention in exchange for loss of K
How do the kidneys sense your BP?
juxtaglomerular apparatus
–> granular cells and macula densa
H2O and Collecting Ducts
H2o is drawn out by osmosis
the rate is determined by the # of aquaporins
permeability to H2o depends on the presence of ADH
ADH helps to bind to CD cells, incorporating more aquaporins into cell membrane, allowing water reabsorption
How does aldosterone reabsorb Na and secrete K?
Aldosterone inserts luminal Na channels, promotes synthesis of Na, K, ATPase in the principal cells of the CDs
Role of aldosterone in K secretion
Final blood K is controlled by aldosterone
–> this only impacts FINAL, not the 90% that is reabsorbed early on in the nephrons
Aldosterone is the ONLY thing that controls K being excreted
Hyperkalemia
could be caused by hypoaldosteronism, renal failure, diurectics, chronic acidosis
you would have low BP, severe cardaic arrthymias, renal failure
Hypokalemia
could be caused by hyperaldosteronism, low potassium diet, diuretics, chronic allkalosis
also would experience hypertension, muscle spasms
Acid-base regulation
Kidneys secrete H+ and reabsorb HCO3
H secretion occurs in proximal tubule in exchange for absorption of Na
Kidneys reabsorb almost all filtered HCO2 and excrete H, so urine is slightly acidic
H is excreted as HPO4 or as ammonia
Relationship of Na, K, and H
Na is reabsorbed from CD, which creates an electrical K to be secreted (Na out, K in)
Plasma K levels indirectly affects plasma H
In severe acidosis, H is secreted at expense of K, which can cause hyperkalemia
Diuretics
drugs that increase urine volume
increases frequency and volume
prescribed for HTN, heart failure, edema
inhibit the reabsorption of salt
classes of strong, weak, potassium sparing
Strongest diuretics
loop and thiazide diuretics
inhibit salt and H2o reabsorption by as much as 25% (lasik)
Potassium Sparing Diuretics
Prevent excessive K+ excretion that tends to occur with above diuretic classes
(spironolactone)
Hypokalemia and Diuretics
–> these diuretics increase Na delivery to DCT, causing increased K loss. Na is reabsorbed, K and H are secreted
If a substance is neither reabsorbed nor secreted…
the amount excreted = amount filtered
would be a perfect measure of GFR
no endogenous substance in the body perfectly fits this criterion
GFR and inulin
inulin = fructose polymer that is neither reabsorbed or secreted
The GFR of inulin equals the clearnce of inulin
GFR = (inulin concentration x rate of urine formation)/plasma concentration
Clearance
volume of plasma from which a substance is completely removed in 1 minute by excretion into urine
we can measure GFR by the clearance of a substance
How can.GFR be measured?
Inulin levels (scientific)
Creatinine levels (clinical)
Creatinine and GFR
filtered and secreted
excretion closely matches GFR, slightly overestimates it
if GFR decreases, plasma creatinine rises–> if kidneys are failing, then the creatinine levels rise
no normal value
Blood urea nitrogen (BUn)
normal = 7-20
higher = kidney disease, heart failure, excessive protein levels
lower than normal = liver failure, low protein, malnutrition
A low eGFR…
high creatinine
high BUN
high albumin in urine
If substance is not filtered
the renal clearance rate = zero
proteins
If substance is filtered, but not reabsorbed or secreted
renal clearance rate = GFR
inulin
If substance is filtered and partially reabsorbed
renal clearnace rate is less than GFR
urea
If substance is filtered and completely reabsorbed
the renal clearance rate is zero
glucose
If substance is filtered and secreted
renal clearance rate is greater than GFR
If substance is filtered, reabsorbed, and secreted
the renal clearance rate is variable
potassium
GFR vs Renal Clearance Rate
GFR specifically focuses on the filtration of plasma through the glomeruli
renal clearance rate encompasses the complete removal of a substance from the blood, considering both filtration and any additional processes that occur in the renal tubules.
GFR is used as an indicator of overall kidney function
renal clearance rate can provide more detailed information about how efficiently the kidneys handle specific substances
