Renal Flashcards
What are the three basic functions of the kidney?
-Homeostatis
-Excretion
-Production
True/False: kidneys are important in regulating total body water?
true
What is the main ion regulating blood volume?
Na
List 5 metabolic waste products removed from the blood
Urea, creatinine, uric acid, allantoin, bilirubin
Under what conditions is renin released?
low arterial blood pressure
What cells release renin?
juxtamedullary
Why is it not uncommon for CKD patients to be anemic as well?
because the kidney releases erythropoietin
What is the preferred substrate for gluconeogenesis in the kidney?
glutamine
Where does gluconeogenesis occur in the kidney?
proximal tubule epithelial cells
What is the body mass: cardiac output ratio of the kidney
<1% body mass to 20% CO
Why does the kidney receive so much of the cardiac output?
because all of the blood needs to be processed by the kidney
What structures are included in the nephron?
renal corpuscle (glomerulus and bowman’s capsule) and the tubules
What is the macula densa, what is its function, where is it located?
a group of cells located in the wall of the distal tubule and its main function is to monitor the amount of NA in the blood, regulate flow rate and blood flow through afferent arteriole
Describe the path blood takes through the kidney
renal artery, afferent arteriole, glomerular capillaries, efferent arteriole, peritubular capillaries (vasa recta), renal vein
What cells make up the tubular system?
a single layer of epithelial cells
True/False: the glomerulus is a high pressure capillary bed
true
What type of capillaries are in the glomerulus?
fenestrated
what can leave fenestrated capillaries?
most solutes and limited amounts of small peptides
What are the 4 main steps of urine formation?
-filtration
-selective reabsorption from filtrate
-selective secretion into filtrate
-excretion of final product=urine
what percent of plasma moves into filtrate?
20%
True/False: kidney osmolarity is higher than plasma? why?
true because the kidney usually reabsorbs more water than dissolved substances
what is the main difference between cortical and justamedullary nephrons
renal corpuscle sits at junction between cortex and medulla and they have longer loops of henle that extend into the medulla
what percent of the blood that goes to the glomerulus gets filtered?
25%
Why can glomerular capillaries have high pressures?
because the goal is filtration of plasma (starlings forces)
Why do peritubular capillaries have low pressure?
because the goal is reabsorption of a large percentage of the filtrate (starlings forces)
True/False: ultrafiltrate contains proteins and blood celss
false. Ultrafiltrate contains water and all the small solutes of blood, but does not have proteins and blood cells
What are the three main layers of glomerular filtration
fenestrated endothelium, basement membrane (basal lamina), podocyte foot processes
What is the purpose of the podocyte foot process?
there are filtration slits that are bridged by nephrin which result in a charged barrier
What is the charge of the barrier created by the glomerular wall?
negative
Describe what will and will not pass the glomerular filtration barrier
-small and/or positively charged particles pass freely
-large and/or negatively charged particles are excluded
What are the roles of mesangial cells
-surround capillary endothelial cells and exhibit contractile characteristics similar to muscle cells
-phagocytic functions
Where does the majority of reabsorption take place?
prox tubule
True/False: proteinurea can be indicative of glomerulus disease
true
Define GFR
the volume of fluid filtered per minute from the glomerular capillaries into bowman’s space
Filtration coefficient is determined by what two factors
permeability and surface area
What two things are true of glomerular capillaries that is not true of capillaries in the rest of the body
-pressure declines only marginally along the length of the glomerular capillary due to flow into a high resistance efferent arteriole
-oncotic pressure increases as more plasma is filtered since protein is left behind
What is the main regulation of GFR
autoregulation which acts on afferent and efferent arterioles
What are the 3 main auto regulation controls
-Myogenic control
-Pressure diuresis
-Tubuloglomerular feedback
Describe myogenic auto regulation
increase in afferent arterial pressure should increase GFR but the myogenic response tempers this response
Describe pressure diuresis auto regulation
increase urine output and Na excretion as a result of an increase in arterial blood pressure which in turn reduces blood pressure and blood volume
Describe tubuloglomerular feedback auto regulation
mediated by the macula densa which senses a flow of filtrate and NaCl in distal tubule, signals juxtamedullary cells to release renin and decreases GFR and RBF`
What factors stimulate renin release?
-drop in blood pressure
-reduced GFR
-reduced concentration of Na and Cl in tubules of kidney
-SNS input to the kidney and circulation catecholamines
Think hemorrhage or dehydration
What are the effects of angeotensin II on GFR and RBF? at high levels vs low levels
- AngII can act on both efferent and afferent arterioles but to different ends whether it is at low levels or high levels
-At low levels preferentially constricts EA
-At high levels constricts AA and EA trying to maintain GFR which results in a small decrease of GFR and RBF, this also leads to a decrease in hydrostatic pressure in peritubular capillaries facilitating reabsorption of ions/ water and maintenance of ECF
What are the factors that inhibit renin release? (7)
-Ang II
-Aldostrone
-ADH
-Renal hypertension
-increased Na or Cl in the distal tubule filtrate
-increased GFR
-ANP
What is the gold standard for GFR measurement?
inulin
What is PAH clearance used to measure?
Measuring of the effective renal plasma flow
Describe filtrate reabsorption in the proximal tubule, what two main methods of transport exist?
paracellular and transcellular.
True/False: paracellular resorption/secretion is always passive?
True
What are the three common mechanisms for regulating channel and transporter activity? What are the speeds of these regualtions?
1.Transport proteins are regulated by translocation (fast)
2.Transport protein levels are regulated by synthesis/degradation (slow)
3.Transport proteins are activated/inhibited by attaching ligands (covalently/reversibly) (slow, but longer acting response)
True/False: glucose transporters in kidney are insulin dependent
False
What glucose transporters are primarily on the apical membrane of the proximal tubule?
sodium dependent (SGLT1&2)
What glucose transporters are on the basolateral membrane of the proximal tubule?
GLUT 1& 2
Where in the nephron is most of the filtered glucose reabsorbed? be specific
S1 of the proximal tubule (~90%)
The rest is absorbed in the S2/S3 as needed
When is glucose excreted in the urine?
during hyperglycemia when Tm is reached
What does Tm stand for when discussing renal resorption?
transport maximum
How does the kidney handle protein and small peptides?
They are filtered to a minor extent, if any gets through they are endocytosed from the filtrate by binding to megalin and cubilin, they are then degraded and the amino acids reenter peritubular blood.
True/False: proteins are not returned intact to peritubular blood
true
How do immunoglobulins get into and not degraded in the renal cells?
they are endocytosed into vesicles which can be transported intact to opposite cellular membrane
How does the kidney handle organic molecules?
endogenous waste products and foreign chemicals that are filtered because they are typically bound to proteins so secretion is the only way to get rid of them (OATs, OCTs) cations are traded for H+ on the apical membrane and anions use MDR1 and MRP2 transporters
What molecules use the MDR1 and MRP2 transporters on the apical membrane of the proximal tubule?
anion based organic molecules
What are two cations that are secreted, but mainly by the distal tubule?
K+ and H+
Why do we care about acidification and alkalization of urine in regards to clearances of certain molecules?
the state of ionization affects the membrane permeability of substances. Unionized substances are more easily reabsorbed than ionized
Describe renal handling of urea
freely filtered
transported in most segments of the nephron
reabsorbed/secreted by diffusion
concentration differences and permeability dictate rate of resorption/secretion
True/False: urea recycling is critical to corticopapillary osmotic gradient/ determining the final osmolarity of urine
True
True/false: thin ascending limb, distal tubule, and collecting ducts are impermeable to urea
true
If glucose fails to be reabsorbed because the renal threshold is exceeded what happens to effective osmotic pressure in the tubular lumen?
osmotic pressure increases
The urine pH can affect both the solubility and reabsorption of weak acids and bases
True
About how much of the total blood volume is filtered per minute?
100mls/min
Why is reabsorption of Na so important? (3)
-Driving force for reabsorption of organic substances
-Driving force for reabsorption of other ions
-Coupled secretion of K and H
True/False: Na homeostasis is important in determining ECF volume
True
What is the main method of Na reabsorption?
Transcellular
Describe Na’s journey from lumen to peritubular blood
-Apical membrane: diffusion through channels or contransported with other molecules
-Basolateral membrane: Pumped into interstitial fluid by Na/K ATPase
-pulled into peritubullar capillaries due to the low hydrostatic
Peritubular capillaries have ____ hydrostatic pressure and ____ oncotic pressure
low, high
What are the contributions of each tubular segment to Na and water reabsorption
Proximal tubule and LOH are the sight of the majority of Na reabsorption
Distal tubules and collecting ducts reabsorb small amounts of both but the major sight of regulation by aldostrone and ADH
Where is the main site of Na reabsorption regulation
Distal tubule and collecting ducts
Where are the tubular locations where water reabsorption is NOT linked to water reabsorption?
LOH
What is the significance of transepithelial potential difference in the early proximal tubule
it is an important in driving Ca2+ and Mg2+ reabsorption and K+ secretion
What is the major anion co transported with Na in the early proximal tubule?
bicarb HCO3-
Describe how bicarb is reabsorbed in the proximal tubule
-H+ is transported into the lumen in exchange for Na
-H+ combines with bicarb to form carbonic acid H2CO3 which can then be broken into CO2 and H2O which move freely into the renal cell
- the cycle then goes backwards to reform bicarb with will be co-transported into the blood with Na
What is the major anion co-transported with Na in the late proximal tubule
Cl-
Describe the water permeability of the LOH
the thin descending limb is permeable and the ascending limb is not
Describe reabsorption of water and Na in the loop of henle
-Thin descending loop has alot of aquaporins so site of water absorption which increases the osmolarity of the filtrate since not alot of Na is reabsorbed here
-The ascending limb is impermeable to water but has Na channels which allows Na to passively transport but will eventually need to be actively transported against its gradient as the environment gets increasingly more hypertonic.
Where is the Na/K/Cl cotransporter
the thick ascending limp of LOH
Why do Ca and Mg passively reabsorb in the think ascending limb?
B/c there is a + lumen potential difference which favors this movement (created by the Na/Cl/K cotransporter)
What is the role of principle cells in the distal tubule and collecting ducts?
regulation of Na/H2O reabsorption thus final concentrations. The Na channels are regulated by aldostrone (increases) and ANP (decreases) while the water permeability is controlled by ADH which adds aquaporins into membranes
Where in the nephron is solute reabsorption occurring at the same rate as water reabsorption
proximal tubule
Where are the locations of K+ reabsorption
-majority is reabsorbed in the proximal tubule as part of isosmotic reabsorption
-Na/K/Cl transporter reabsorbs 20% in thick limb
Where does regulation and secretion of K+ occur?
distal tubule and collecting ducts
What cell in the proximal tubule is responsible for K reabsorption?
intercalated cell
What cell in the distal tubule and collecting duct is responsible for K secretion/Na reabsorption?
principal cell
How does aldostrone regulate K+ secretion?
-it increases K channels
-it activates the Na-K ATPase which reabsorbs Na and secretes K
What three molecules are responsible for Ca regulation
-Parathyroid hormone
-calcitonin
-vitamin D
What forms of Ca exist in the blood? what form is freely filtered?
bound and ionized, only ionized/unbound is filtered
Where is the majority of Ca2+ reabsorbed? is it passive or active?
the proximal tubule, passive due to solute drag paracellularly
Where is the only location to regulate Ca2+ handling? by what hormones?
The distal tubule by PTH which inserts Ca channels into the apical membrane and Vit D which (with PTH) activate Ca ATPase in the basal membrane
Where is P reabsorbed? How?
Proximal tubule passively and thick descending by Na/P co-transporter which is negatively regulated by PTH (encouraging excretion)
Where is the site of the majority of Mg2+ reabsorption?
Thick ascending limb
What are the ranges for Hyposthenuric, isothenuric, and hypersthenuric USG?
Hypo <1.008
Iso 1.008-1.012
Hyper varies by species but dog is >1.030, cat is >1.040, horse >1.020
What are the mechanisms and sites of water reabsorption
- paracellularly in proximal tubule and think descending limb
-transcellularly in the distal tubule under the regulation of ADH
What are the 3 main roles of ADH
-increase water permeability of principle cells of the late distal tubule and collecting ducts
-increase urea permeability in the inner medullary collecting ducts enhancing urea recycling
-Increased Na/K/2Cl transporter in thick ascending limb enhancing countercurrent multiplication
What two things create the corticopapillary gradient?
-countercurrent multiplication of the LOH that deposits NaCl deep in the medulla
-urea recycling by the inner medullary collecting ducts
Where in the nephron is the osmolaroty of the tubular filtrate highest?
Medullary portion of the LOH
Central diabetes insipidus is a condition in which the posterior pituitaty fails to secrete ADH. in an animal with this condition what type of urine do you expect
hyposthenuric
Relative proportion of water in ECF/ICF is influenced by what ion? Why?
Na, because it does not readily cross cell membranes
What are the two major (general) regulators of Na+ excretion/reabsorption?
Changes in tubular resorption and changes in GFR
What is the RAAS system mainly activated by?
hypovolemia due to hemorrhage or dehydration
What is the affect of angiotensin II on Na reabsorption in the proximal and distal tubule
-Prox: stimulates reabsorption by activating Na/K ATPase and Na/H exchange
-Dist: stimulates Na channels and Na/Cl symporters
What effect, if any, does aldostrone have on K?
It promotes secretion into filtrate
What are the 6 main determinants of urine volume?
-resorption of solutes
-RAAS
-ADH
-SNS
-Blood Pressure
-Protein oncotic pressure
Describe the neural innervation of the bladder
-Sympathetic (storage): contraction of internal urinary sphincter and relaxation of detrusor muscle which allows bladder to fill without emptying
-Parasympathetics (emptying): contraction of the detrusor muscle, relaxation of the internal urinary sphincter
-Somatic (voluntary): maintain tonic contraction of external urinary sphincter until voluntary inhibition
Briefly describe the micturition reflex
-bladder is full stimulating stretch sensitive fibers
-once threshold is reached, a reflex causes contraction of detrusor
-high pressure opens the IUS along with PNS mediated relaxation which opens the neck of the bladder
-simultaneously another reflex inhibits activity of the somatic fibers which hold the EUS closed
-urination
What would happen if there was damage to the sacral region of the spinal cord?
the bladder will be large and fail to empty
What is the major waste product resulting from protein catabolism in fish?
ammonia
What causes marine fish to have blood that is isotonic with sea water?
high levels of urea in the blood
Which animals have a renal portal system?
bony marine fish, amphibians, freshwater fish, birds
What animal stores excess water in the bladder for when they need it?
Amphibians
What animals excrete uric acid as waste product?
retiles and birds
