Renal Physiology Flashcards
1
Q
Main function of the kidneys
A
deal with the way the plasma has to be processed/handled
- plasma = water (majority), ions, organic molecules such as proteins, glucose, AAs, etc. + blood glasses dissolved in it
2
Q
ECF
A
- 20%
- fluid outside of the cell; plasma + interstitial fluid + CSF
3
Q
Plasma
A
liqui, non-cellular part of blood, fluid found inside blood vessels
4
Q
Chemical nature of molecules plays a role in diffusion
A
- polar: generally unable to diffuse across membrane bilayer (AAs, glucose, water)
- non-polar: diffuse rapidly (CO2, fatty acids, steroids)
5
Q
Diffusion of water through cell membrane
A
- polar molecule
- rate of water diffusion is variable
- depends on aquaporins (water channels)
- water concentration in a solution is measured in:
> osmoles: 1 osmoles (osm) = 1 mole of solute particles
> osmolarity: number of solutes per unit volume of solution expressed in mols/L
6
Q
Net diffusion of water across a selectively permeable membrane from a region of high water concentration to one with a lower water concentration
A
Osmosis
7
Q
The pressure necessary to prevent solvent movement (osmosis) is known as
A
the osmotic pressure of the solution
8
Q
Tonicity
A
determined by the concentration of non-penetrating solutes (NPS) of an extracellular solution relative to the intracellular environment of a cell
- the solute concentrations may influence changes in cell volume
9
Q
Isotonic
A
- isosmotic
- same concentration of NPS outside and inside of the cell; cell volume do not change
10
Q
Hypertonic
A
- hyperosmotic
- higher concentration of NPS outside than inside of the cell; cells shrink
11
Q
Hypotonic
A
- hyposmotic
- lower concentration of NPS outside than inside of the cell; cells swell
12
Q
Normal osmolarity inside a cell
A
~300 mOsm/L
13
Q
Movement of solute/water out of blood (plasma)
A
filtration
14
Q
Movement of solute/water into the blood (plasma)
A
absorption
15
Q
Factors determining fluid movement along capillaries
A
- capillary hydrostatic pressure (Pc)
- interstitial fluid hydrostatic pressure (Pif)
- osmotic force due to plasma protein concentration (pi-c)
- osmotic force due to interstitial fluid protein concentration (pi-if)
Net filtration pressure = Pc +pi-if - Pif - pi-c
**cap hydrostatic pressure = very low at venous end - quite a bit of filtration at arterial end of caps and at venous end = pressure becomes negative so absorption of fluid from the interstitial space into caps
16
Q
Location of kidneys
A
retroperitoneal
17
Q
Micturition
A
peeing; released from bladder to outside ; involves ANS
18
Q
Renal corpuscle
A
- blood filtering component of kidneys > glomerulus and Bowman's capsule - the tubule lined with epithelial cells - cells in each segment vary in structure and function along the length of the tubule - based on the tasks it has to perform
19
Q
Filtering unit
A
allows blood to flow through glomerular capillaries = protein, cell free fluid that filters from glomerulus to bowman’s space
20
Q
Development of Renal Corpuscle
A
Stage 1: nephrons develop as blind-ended tubules composed of single layer of simple epithelium
Stage 2: growing tuft of capillaries penetrate the expanded end of tubules
a) basal lamina is trapped in between endothelial cells of capillaries and epithelial layer
b) epithelial cell layer differentiates into parietal (outer) and visceral (inner) layer
Stage 3: parietal layer eventually flattened to become wall of Bowman’s capsule; visceral layer becomes podocyte cell layer
21
Q
T or F. All the renal corpuscles are found in the cortex
A
T
22
Q
Two types of nephrons
A
- cortical: 85%; basic functions
> short loop of Henle which may dip into medullary portion and sometimes may not even find them there, just have short loop found in cortical area; basic function is filtration and going through reabsorption process, secretion, etc. - juxtamedullary: 15%; basic functions; regulate the concentration of urine
> although located in cortical part, located closer to boundary part of medulla and cortex; long loop of Henle which dips down to the medulla and there’s a reason why they are there - basic functions AND regulating conctn of urine (produce dilute urine or more concentrated and give out v little water when urine is formed
23
Q
Blood supply around the nephron: 3 types of capillaries
A
- glomerular: sits within Bowman’s cup; in flow of blood from afferent arteriole
- peritubular: goes around proximal tubule (around cortical nephrons); eventually renal vein and takes blood out from the kidneys
- juxtamedullary nephrons has no peritubular capillaries but vasa recta instead; formed when efferent arterioles come out of corpuscle continues on into medullary portion and gives out long branches of capillaries around loop of Henle ; found almost in parallel and around loop of Henle in the juxtamedullary nephron
24
Q
Substances moved from peritubular capillary plasma into tubular lumen
A
secretion
25
Sometimes, whatever filtrate has entered and is moving through the renal tubule, some of that or maybe all can move from tubular lumen back to the plasma (peritubular cap plasma or blood is flowing)
reabsorption
26
T or F. all substances will go through secretion in nephron
F, not all substances are treated equally in the nephrons .. will go through filtration but not all of them will necessarily go through secretion or all of them will go through reabsorption …secretion but no reabs or only reabs and no secretion, etc.
- ex: glucose for a healthy indiv gets filtered at glom capillaries but does not get secreted but entire amount is actually reabsorbed = useful for ATP so no excretion
27
Large proteins or albumin are held back because: (3)
- pore sizes are not large enough to allow passage
- pores and BM have negative charges and repels negatively charged proteins
- podocytes have slits that remain covered with fine semi-porous membranes
28
Ultrafiltrate
when things get filtered, whatever was in the plasma, pretty much most of it gets into Bowman's space; filtrate that gets into Bowman's space pretty much same conctn of stuff that got into afferent arteriole --- hence = ultrafiltrate (pretty much contains all the stuff that entered plasma other than the blood cells and large proteins, etc.)
29
Proteinuria
pathophysiology condition; nephritis; mutation; when there is something that has gone wrong with filtration barrier and as a result = large proteins end up in Bowman's space as well as filtrate so whenever you find protein in urine -- proteinuria
30
What is filtered through the glomerulus?
```
water
electrolytes
glucose
amino acids
fatty acids
vitamins
urea
uric acid
creatinine
```
31
What is turned back form the glomerulus?
blood cells
plasma proteins
large anions protein-bound minerals and hormones
most molecules > 8 nm in diameter
32
Glomerular filtration rate (GFR)
- volume of fluid filtered from the glomerulus into the Bowman's space per unit time
33
Factors influencing GFR
1) net glomerular filtration pressure
2) permeability of the corpuscular membrane
3) surface area available for filtration
4) neural and endocrine control
34
Mesangial cells on GFR
- not part of the filtration layers
- not part of the JGA (juxtaglomerular apparatus)
- contraction of these cells reduce SA of the glomerular capillaries
- GFR decreased
35
GFR regulation
- myogenic response (similar to autoregulation in other systemic arterioles)
- tubuloglomerular feedback: a role of juxtaglomerular apparatus (JGA)
> increased tubular flow causes constriction of the afferent arteriole to reduce GFR
> regulated by paracrine actions on the juxtaglomerular apparatus
> paracrine control of afferent arteriole resistance
- hormones and autonomic neurons (by changing resistance in arterioles)
36
Substance excreted in urine < filtered load
reabsorption as filtrate was going through the renal tubule; although it was filtered, some was reabsorbed
37
Substance excreted in urine > filtered load
secretion during process occurred; substances were added
38
T or F. Amount filtered is much larger than what is found in the body
T! Large portion is reabsorbed for water, sodium and glucose = essential for body's needs and purposes
Not like urea
39
T or F. Physiological regulation mostly happens w water
T! glucose = no physiological regulation under healthy conditions
** in terms of regulation, some of them are physiologically regulated = endocrine or hormonal control where amounts reabsorbed can be altered to change homeostatic range **
40
Reabsorption
when there are substances that have come in to tubular lumen by filtration; some of these substances can be once again taken from tubular lumen back to plasma flowing through the peritubular capillary
41
At normal plasma glucose concentration, the clearance of glucose is ____.
zero
| - all the filtered glucose is reabsorbed
42
In the proximal tubule, glucose is reabsorbed by:
- secondary active transport on the luminal side of SGLT
- facilitated diffusion on the basolateral side using carrier protein GLUT
* * from tubular lumen to plasma of peritub caps **
43
Above renal threshold glucose appears in the urine
glucosuria
44
Reabsorption of glucose is closely linked to...
Na+ reabsorption
| - need to have Na+ reabsorbed for glucose reabsorption
45
Filtration rate of glucose
with increasing plasma glucose conctn, filtration happens across the glom capillaries and the filtered load = linear increase
46
Reabsorption rate of glucose
as glucose conctn increases = straight increase in reabsorption; then at certain point = max reabsorption, rate = plateaus = transport maximum = shows u that this is a mediated transport that happens for glucose during reabsorption
- when these transporter proteins get saturated, can no longer pick up glucose from the lumen and reabsorb it into the peritubular caps = absolutely saturated and reach transport max
- 100-200 mg/100 mL plasma is approximate normal range
- Transport maximum (Tm) = 375 mg/min
47
Excretion rate of glucose
if our plasma glucose conctn increases beyond 300 mg/ 100 mL plasma (renal threshold), the reabsorption not only stops but the glucose starts appearing in urine = excreted; glucose urine excreted starts increasing linearly
48
Appearance of glucose in urine
diabetes mellitus
renal glucosuria
- whenever threshold level is excreted and the filtered level is very high, glucose cannot be reabsorbed and as a result, glucose is in urine
49
Diabetes mellitus
capacity to reabsorb glucose is normal, but filtered load is greatly increased and is beyond the threshold level to reabsorb glucose by the tubules
50
Renal glucosuria
- genetic mutation of the Na+/glucose cotransporter, that normally mediates active reabsorption of glucose in the proximal tubules
- AKA benign glucosuria or familial renal glucosuria
51
Tubular secretion
- tubular secretion is also coupled to reabsorption of Na+
- involves active transport
- mostly H+ and K+
- choline, creatinine, and penicillin
* * creatinine while behaves like inulin, only secreted very slightly **
52
Renal Clearance
- a way of quantifying kidney function in removing substances from plasma
- measure of the volume of plasma from which a substance is completely removed by the kidney/unit time
- unit for clearance = ml/min or L/h
- every substance has distinct clearance value
53
Clearance of inulin
- polysaccharide, not found in the body
- readily filtered, but not reabsorbed, secreted, or metabolized by the tubule
- Cin = 7.5:/h = 180L/day = GFR
- Cin can be used to measure GFR; can measure filtration rate of nephrons using clearance rate of inulin
54
Clearance of creatinine
- product of muscle metabolism
- creatinine can be used to measure GFR clinically
- filtered, not reabsorbed, but undergo slight secretion
- clearance of creatinine slightly overestimates GFR, but can be used clinically
* * can't inject patient with inulin to look at kidney functions so look at creatinine **
55
Division of labour in different segments of the tubules
- proximal convoluted tubule: reabsorbs most of the water and non-waste plasma solutes; major site of solute secretion except K+
- loop of Henle: creates osmotic gradient; reabsorbs large amounts of ions and less amounts of water (by absorbing ions, deposits ions in interstitial space and creates an osmotic gradient)
- distal convoluted tubule: major homeostatic mechanisms of fine control of water and solute to produce urine
56
Water reabsorption
- water moves via diffusion across water channels (aquaporins)
- large volume (~67%) of water reabsorbed in the proximal tubules
> aquaporins are always open in the PCT
- water reabsorption is dependent on NA+ reabsorption
- osmotic gradient set up by NA+ reabsorption acts as the driving force
57
Cells lining these are under physiological control
cortical collecting and medullary collecting ducts
- vasopressin or antidiuretic hormone
- this hormone regulates a specific type of aquaporin
- takes place in the cells of the collecting ducts
58
Decrease in osmolarity = increase in water conctn in that area
(Na+ moves downhill into interstitial fluid)
as a result, bc water conctn increased in lumen compared to cell or interstitial fluid; through open aquaporin.. water can move by osmosis to interstitial fluid and through there it goes to peritubular cap cells (BULK FLOW)
59
Water transport in the loop of Henle
- water reabsorption through thin descending portion of loop
- salt reabsorption through thick ascending portion of loop; ascending limb impermeable to water!!! (only salt is absorbed to peritub caps)
60
Long loop of Henle
(ex: Kangaroo rat) gradient is wider range in desert animal where water conservation is essential = steep gradient!!!
61
How does the vasa recta help the counter-current exchange?
1. blood flow in the vasa recta serve as counter-current exchangers
- helps in maintaining the Na+ and Cl- gradient
- gradient is not washed away (like straight vasa recta)
2. blood flow in medulla is low
- less than 5% of the total renal blood flow and is sluggish
- prevents solute loss
3. the capillaries are freely permeable to ions, urea, and water and they move in and out of the capillaries in response to the concentration gradients
- vasa recta does not create medullary hyperosmolarity, but prevents it from being washed out, and therefore maintains it
62
Counter-current exchange in vasa recta
- vasa recta permeable to salt, urea, and water
- NaCl move out of the ascending limb, interstitium, to enter the descending limb as blood enters the descending limb of vasa recta
- water diffuses out of the descending limb into the ascending limb
- this mechanism reinforces the gradient created by the renal tubules by exchange of salt and water
- leads to increase in Na+ and urea concentration in the renal medulla interstitial space
63
Recycling and trapping of urea
- 50% of urea is reabsorbed in the proximal tubule
- 50% is secreted back into loop of Henle
- 100% urea re-enters distal tubule
- 30% reabsorbed again from the CCD
- 55% reabsorbed from the IMCD (due to ADH secretion)
- only 5% diffuses out to vasa recta and another 50% recycled (secreted) back into tubule
- minimal uptake of urea by vasa recta and recycling urea in the interstitial space helps in maintaining high osmolarity in the medulla
- 15% of the original amount is excreted (much less than the filtered amount)
64
T or F. As we go from top to bottom, our osmolarity increases and not just due to NaCl but also due to trapping of urea
T, 100% of urea found in Bowman's space
65
Why is there a need for concentrated urine?
kidneys save water by producing hyperosmotic urine
66
Mechanisms used to maintain the hyperosmotic environment of the medulla: 5
1. counter-current anatomy and opposing fluid flow through the Loop of Henle of the juxtamedullary nephrons
2. reabsorption of NaCl in ascending limb
3. impermeability of ascending limb to water
4. trapping of urea in medulla
5. hairpin loops of vasa recta maintains the hyperosmotic interstitium in medulla
* * ADH regulates water reabsorption in collecting duct **
67
ADH/vasopressin
- peptide hormone (fast acting)
- osmoreceptors (hypothalamus) sense INCREASE in plasma osmolarity
- produced by cells of the SON of the hypothalamus
- secreted from the posterior pituitary
* * super optic nuclear cells produce ADH - carried by neuronal cells to posterior pituitary then released from there **
- > also works on vasculature and controls BP
68
water channels found in renal tubule cells (nephrons) and other cells
aquaporins
- 1 in PCT
- 2, 3, 4 in collecting ducts
- AQP2 insertion on the luminal side is regulated by ADH via AQP2 gene transcription
- AQPs on the basolateral membranes are NOT regulated by ADH
69
In the absence of ADH...
collecting duct cells are almost impermeable to water; more water reabsp from lumen into peritub caps
= extreme loss of large fluid volume in the urine; pee a lot!!! (water diuresis)
70
Diabetes insipidus
1. central: failure to release ADH from posterior pituitary gland
2. nephrogenic diabetes insipidus: inability to concentrate urine due to impaired renal tubule response to vasopressin (ADH), which leads to excretion of large amounts of dilute urine; can be inherited or occur secondary to conditions that impair renal concentrating ability
71
Relationship between body fluid volume and [Na+] regulation: (7)
1. water reabsorption is dependent upon Na+ reabsorption
2. distribution of water in the fluid compartment is dependent on the solute concentration
3. [Na+] and extracellular body fluid volume are closely linked
4. plasma osmolarity mainly determined by measuring the plasma Na+ concentration
5. any changes in total body [Na+] cause changes in blood volume and blood pressure
6. volume of water reabsorption dictates how much water will be excreted
7. physiological control of water reabsorption/excretion is exerted by ADH/vasopressin
72
Nerve endings that are sensitive to stretch
baroreceptors
| - located at carotid sinus, aortic arch, major veins, and intrarenal (JG cells of JGA)
73
used for short-term regulation of low plasma volume (reflection of low sodium level)
baroreceptors
74
How do baroreceptors work?
- they sense changes in blood volume, peripheral resistance
- increase/decrease in BP causes increase/decrease in stretch = increase/decrease in nerve impulse frequency
- activation of SYM branch of the ANS
- constriction of afferent arteriole
- decrease GFR, decrease Na+ filtered, and less Na+ excreted
75
T or F. We don’t actually have receptors specifically for Na+ regulation
T! we use baroreceptors instead (part of CV; detect fluid volume)
76
Long-term regulation of low levels of Na+
- Aldosterone: a steroid hormone secreted from the adrenal cortex
- low Na triggers its synthesis and secretion
- effect is long-term
- site of action: late distal tubule and CCD
77
Actions of aldosterone
a) induces synthesis of Na+ transport protein
b) stimulates Na+ reabsorption
c) reduces Na+ secretion
** reverses level of sodium = takes a while to work .. goes through gene transcription, etc. = long term change **
78
T or F. Aldosterone helps with insertion and maintaining levels some of the channel proteins (Na to get into cell)
T!
79
What controls aldosterone secretion?
- low total body [Na+] stimulate secretion of aldosterone
| - angiotensin II acts on adrenal cortex to control secretion of aldosterone
80
Renin
secreted from the juxtaglomerular cells of the JGA in kidney
81
What determines [renin] plasma?
1. sympathetic input from external baroreceptors
2. intrarenal baroreceptors
3. signals from macula densa
82
The most important trigger for the release of aldosterone is the renin-angiotensin mechanism, initiated in response to: (3)
1. sympathetic stimulation of renal nerves
2. decrease in filtrate osmolarity
3. decreased blood pressure
83
senses decreased intrarenal pressure
intrarenal baroreceptors
84
What stimulates ANP secretion
1. increased Na+ concentration
2. increased blood volume
3, atrial distension!! [whenever blood vol goes up = atrial distension caused is sensed (made by cardiac atria in response to distension of atria due to blood vol)]
85
Where is ANP made?
synthesized and secreted by cardiac atria
86
Sites of ANP action
- on cells of several tubular segments
- ANP inhibits aldosterone actions
- inhibits Na+ reabsorption
- increases GFR and Na+ excretion
87
T or F. Secretion of K can also happen in collecting duct area
T! when blood K levels went up = like too many bananas = excess K = hyperkalemia = increasing levels of excretion
** most filtered K+ is reabsorbed **
88
Regulation of K+ balance
- most of the filtered K+ is reabsorbed in the proximal tubule and loop of Henle
- collecting duct can secrete a small amount of K+
- [K+] in urine is regulated in the cortical collecting duct
89
Excess K+ in blood
hyperkalemia
90
What controls homeostasis of K+ in the body?
Aldosterone secreting cells in adrenal cortex are sensitive to extracellular [K+]
91
pH for ECF
between 7.35 and 7.45
- acidosis if arterial plasma pH <7.35
- alkalosis if arterial plasma pH >7.45
92
Why is balance of H+ important for body functions?
- small changes in pH cause proteins to change shape
a) enzymes are protein in nature and shape changes can alter their activity
b) changes in neuronal activity
c) coupled to K+ imbalances
d) irregular cardiac beats
- pH <6.8 and >7.8 is fatal (death)
93
Volatile acids
CO2
- vapour condition/gaseous at room temp = volatile
- carbonic acid = dissociates to yield CO2 = gas at room temp = volatile
94
Nonvolatile acids
organic and inorganic acids from other sources than CO2
- phosphoric acid, sulfuric acid (metabolism of sulfur-containing AAs = cysteine, methionine = produces sulfuric acid)
- metabolism of lysine, arginine, and histidine produces hydrochloric acid
95
How is H+ buffered in the body?
- most of the H+ are buffered by extracellular or intracellular fluid
- CO2/HCO3- is the extracellular buffer system
- phosphate ions and proteins are intracellular buffers
> hemoglobin is an intracellular buffer
96
What is a buffer?
- any substance that binds to H+ is called a buffer
- buffer + H+ = Hbuffer
- a buffer is composed of a weak acid and its conjugate base
- buffers modify or adjust the change in pH following the addition of acids or bases
97
What causes respiratory imbalances?
- hyperventilation, hypoventilation, respiratory malfunction causes H+ imbalance
- if imbalance due to non-respiratory causes, then ventilation is changed by reflex to adjust the imbalance
> increase [H+] stimulates ventilation
> decrease [H+] inhibits ventilation
98
Reabsorption of HCO3-
- dependent on H+ secretion
- active process (uses ATP)
- normally most of the HCO3- is reabsorbed
- occurs in the proximal tubule, ascending loop of Henle, and CCD
- transport mechanism of H+ is different depending on part of the tubule segment
99
T or F. H+ is secreted outside of nephron or in urine
F! instead, absorbed by bicarbonate coming through filtrate => CO2 and H2O which can be released ; no loss or gain of bicarbonate bc secreted one to the interstitial fluid
- excess H+ combines with ECF bicarbonate = kept in check
100
Response to acidosis: when excess H+ is secreted than there is HCO3- in lumen to bind H+
1. extra H+ binds to HPO4 2-
2. HCO3- is still generated by tubular cells and diffuses into plasma
3. NET gain of HCO3- in plasma
OR
1. cells from proximal tubule are only involved
2. uptake of glutamine from glomerular filtrate or peritubular plasma
3. NH4+ and HCO3- are formed inside cells
4. NH4+ actively secreted via the Na+/NH4+ counter transport into the lumen
5. HCO3- is added to plasma
101
Respiratory acidosis
- occurs as a result of decreased ventilation
- increased blood PCO2
- occurs in emphysema
- kidney compensates by secreting H+ and lowers plasma [H+]
102
Respiratory alkalosis
- occurs as a result of hyperventilation
- decreased blood PCO2
- happens in high altitude
- kidney compensates by excreting HCO3-
103
Metabolic acidosis
- occurs in diarrhea (loss of bicarbonate ions)
- severe exercise
- diabetes mellitus
- results in increased ventilation
- results in increased H+ secretion
104
Metabolic alkalosis
- occurs after prolonged vomiting
- results in decreased ventilation
- results in increased HCO3- excretion
