Physiology Midterm 2 Flashcards
What is the number role of the kidneys?
Regulation of extracellular fluid volume and blood pressure
Role of the kidney?
- Regulation of extracellular fluid and blood pressure 2. Regulate plasma osmolarity 3. Regulates ion balance 4. Regualtes plasma pH 5. Excretion of waste (endogenous and exogenous) 6. Endocrine (erythropoietin and renin and Ca2+ homesostasis)
Location of a cortical nephron?
Stays in the cortex of the kidney
Location of a juxtamedullary nephron?
Dives down from cortex into the medulla of kidney
How many portal systems are there in the body?
3 (2 capillary beds…hypothalamus/ant. pit. and kidney and liver)
Renal portal system for a cortical nephron?
Renal artery, branches of smaller arteries then arterioles in cortex, afferent arterioles, glomerular capillaries, efferent arterioles, peritubular capillaries, venules, veins, renal vein, vena cava
Renal portal system for a juxtamedullary nephron?
Renal artery, branches of smaller arteries then arterioles in cortex, afferent arterioles, glomerular capillaries, efferent arterioles, peritubular capillaries, vasa recta, venules, veins, renal vein, vena cava
What is the juxtaglomerular apparatus?
Association between ascending limb of Loop of Henle and afferent/efferent arteriole
What is the renal corpuscle?
Glomerulus and Bowman’s capsule
How much plasma does the kidney process per day, and how much urine is excreted?
180 L/plasma per day and 1.5L urine/day
How much of the fluid that passes through the kidneys reabsorbed?
99%
Where does filtration happen in the kidney?
Renal corpuscle (glomerulus and Bowman’s capsule)
Equation for the amount of urine excreted?
Amount filtered - amount reabsorbed + amount secreted = amount excreted
Where is the filtrate from the kidney most similar to plasma?
At the renal corpuscle…the only thing that is different is it doesn’t have blood cells and less protein
Where does iso-osmotic reabsorption occur?
The proximal tubule (70% of fluid and solute is reabsorbed)
By the time the fluid in the kindeys gets to the ascending loop of Henle, how much of the filtrate has been reabosorbed?
90%
Where does reabsorption happen in the kidneys?
All along the peritubular capillaries from the proximal tubule to the collecting duct
Where does fine tuning and water/salt balance and endocrine control happen in the kidney?
The distal tubule/collecting duct
How much of the plasma moves out of the glomerular capillaries into the tubules?
approximately 20%, with the rest entering the efferent arterioles
What is the filtration fraction?
% of total plasma volume that enters into tubule
Barriers to filtration in the renal corpuscle?
Glomerular capillary endothelium, basement membrane, epithelium of Bowman’s capsule
How does the endothelium of glomerular capillaries create a barrier to filtration?
The fenestrated capillaries allow most substances to pass except for blood cells and most proteins (repelled by negatively charged proteins on pore surfaces)
How does the basement membrane act as a barrier to filtration in the renal corpuscle?
It is a layer of ECM between capillary endothelium and epithelium of Bowman’s capsule. It acts as a coarse sieve, keeping most proteins in plasma
How does the epithelium of Bowman’s capsule act as a barrier to filtration?
It has gaps between foot processes of podocytes that leave narrow slits close my semi-porous membrane
What are the 2 unique proteins that are expressed of the membrane of the filtration slits in the kidney?
Nephrin and podocin
What force is driving filtration in the glomerulus?
Hydrostatic pressure and the leakiness of the barrier keep net filtration HIGH…GFR = 180 L/day, plasma volume is approx. 3 L
Factors that influence GFR?
Net filtration pressure and filtration coefficient (surface area of glomerular capillaries and permeability of the interface)
Is GFR influences by changes in blood pressure?
NO, lots of autoregulation
If the resistance in the afferent arteriole of the kidney increased what would happen?
Renal blood flow would decrease, hydrostatic blood pressure would drop, lowering GFR
What would happen if resistance in the efferent arteriole in the increased?
Renal blood flow would decreases, but hydrostatic increases, which INCREASES GFR
Why does blood pressure have to be regulated so heavily in the kidneys?
High pressures will damage glomerulus capillaries
What is the myogenic response in the kidneys?
Intrinsic response of arteriole smotoh muscle to pressure changes. Vasoconstriction in response to increased blood pressure
What is tubuloglomerular feedback?
- Increase in GFR 2. Increased flow through tubules 3. Increased flow of NaCl past macula densa 4. Paracrine signal from macula dense acts on afferent arteriole 5. Afferent arteriole constricts 6. Decrease in renal blood flow 7. Decrease in hydrostatic pressure 8. Decreased GFR
What is the juxtaglomerular apparatus?
Area in nephron where ascending loop of Henle/distal tubule, afferent and efferent arterioles are close to one other. Comtains the macula densa and granular cells that help to regulate GFR
Autonomic effects on GFR that can override the myogenic response and tubuloglomerular feedback in the kindeys?
Sympathetic innervation of afferent and efferent arterioles that in extreme conditions (severe dehydration and bleeding out) causes a sympathetic vasoconstriction due to a drop in blood pressure, which will decrease GFR
Endocrine effects on GFR?
Angiotension II (potent vasoconstrictor) and Prostaglandins (vasodilators). Bothe can also affect the filtration coefficient through actions on podocytes (alter size of slits) and mesengial cells (shapes of glomerular capillaries)
Why doesn’t the kidney only filter the 1% that is excreted?
Filtration removes foreign/toxic substances in addition to endogenous materials (high rate of filtration quickly clears these substances) and filtering ions and water simplifies their regulation (material reaching distal tubule that is not needed for homeostasis passes into urine)
Steps in governing tubular reabsorption?
- Na+ is reabsorbed by active transport 2. Electrochemical gradient drives anoin reabsorption 3. Water moves by osmosis, following solute reabsorption. Concentrations of other solutes increase as fluid volume in lumen decreases 4. Permeable solutes reabsorbed by diffusion through membrane transporters of by paracellular pathways
Paracellular pathway in kidneys?
Molecules through cell-cell junctions
Epithelial/trans-cellular transport in kidneys?
Cross of the apical and basolateral membranes of epithelial cells. Mechanism depends on driving force…down gradient = leak channels or facilitated diffusion and against gradient = primary or indirect active transport
Steps in active transport of Na+ in proximal tubule?
- Na+ enters cell through various membrane proteins, moving down its electrochemical gradient 2. Na+ pumped out basolateral side of cell by N+/K+ ATPase
Steps in Na+ - Linked Reabsoprtion?
- Na+ moving down its electrochemical gradient uses SGLT transporter to pull glucose into the cell against its concentration gradient 2. Glucose doffuses out basolateral side of cell using GLUT protein 3. Na+ pumped out by Na+/K+ ATPase
How are amino acids, lactate, Krebs cycle intermediates, phsophate, and sulphate reabsrobed?
Apical symporter + basolateral facilitated diffusion carrier or ion exchanger
Steps in the passive reabsoprtion of urea?
- Na+ and other solutes reabsorbed at proximal tubule (via ENaC, Na+/K+ ATPase) 2. Water follows by osmosis 3. Loss of water from tubular fluid results in higher urea concentration in tubule 4. Urea moves passiviely out of tubule through epithelial cells into ECF (paracellular route)
What is the renal threshold?
Plasma concentration of a substance at which Tm occurs
How is interstitial fluid able to be reabsorbed into the peritubular capillaries?
Lower hydrostatic pressure in the peritubular capillaries results in net reabosprtion of interstitial fluid
What is secretion in the kindeys?
Transfer from the extracellular fluid to tubular fluid…very specific and depends on membrane transporters
What are the major ions that are secreted for homeostatic regulation?
K+ and H+…endogenous materials and xenobiotics are also secreted
Steps in the secretion of organic anions at the proximal tubule?
- Direct active transport. The Na+/K+ ATPase keeps the concentration of intracellular Na+ low 2. Secondary indirect active transport. NaSC cotransportoer concentrates dicarboxylate inside the cell using energy stored in Na+ concentration gradient 3. Tertiary indirect active transport. Basolateral OAT transporters concentrates organic anions (OA-) inside cell, using energy stored in dicarbodylate gradient
What is a naDC?
Na+-dicarboyxylate cotransporters on both the apical and basolateral membranes. Transports dicarboxylates such as citrate, oxaloacetate and alpha ketoglutarate
Organic anion transporters?
Able to transport range of anions…endogenous (bile salts) and exogenous (benzoate, salicyclate, and saccharine)
Composition of urine versus filtrate?
Glucose, AAs, proteins, and other useful metabolites gone. Waste products much more concentrated (water and ions variable depending on needs)
Formula for clearance from the kidney?
Clearance = excretion rate of X (mg/min) / concentration of substance in plasma (mg/mL)
What molecules are used as indicators of GFR?
Inulin and creatinine
Less of substance in urine than filtered?
Net reabsorption
More of substance in urine than was filtered?
Secreted
No change in the amount that was filtered and what is in urine?
Only filtration
Formula for filtration of a substance?
Concentration of substance in plasma x GFR
Opening between bladder and urthera is guarded by what 2 sphincters?
Internal – smooth muscle (continuation of bladder wall) External – skeletal muscle (tonic stimulation from CNS keeps it closed most of the time)
The simple spinal reflect of micturitoin (urination)?
Bladder fills, activates stretch receptors, afferent information travels to spinal cord and activates 2 sets of neurons, parasympathetic (acts on smooth muscle of bladder) and somatic (inhibits motor neurons to external sphincter)
Ions that kidney helps maintain homeostatic levels of?
Na+, Ck-, K+, H+, Ca2+, HPO42-, HCO3- (ECF volume and osmolarity)
Can the kidney replace lost water?
NO! Drinking is the only way to replace lost water, and the kidney can only conserve water.
Response to decreased blood volume and blood pressure?
Volume receptors in atria and carotid/aortic baroreceptors decrease firing rate. Trigger homeostatic reflix. Cardiovascular system decreases CO and vasoconstricts blood vessels. Increase thirst increases ECF and ICF. Kindeys conserve H2O to minimize further water loss.
Response to increased blood volume and blood pressure?
Volume receptors in atria, endocrine cells in atria, and carotid and aortic baroreceptors increase firing rate. Triggers homeostatic reflex. Cardiovascular system decreases CO and causes vasodilation. Kindeys excrete salts and water in urine to decrease ECF and ICF volume, both of which decrease blood pressure.
Amount of water gained throughout the day?
2.2 L from food/drink and 0.3 L/day from metabolism (aerobic respiration produces Co2 and H2O)
Amount of water lost throughout the day?
Insensible water loss from lungs and skin 0.9 L/day, urine 1.5L, and feces 2.5L
Water balance in the body?
0 L
Diuresis occurs because?
Need to eliminate excess water = dilute pee = 50 mOsM
Extremely concentrated urine occurs when?
Body needs to conserve water (antidiuretics)
How does water cross cell membranes?
Leaks through lipid bilayer (happens in most cells but doesn’t explain the rapid movement through some cells) and travels through aquaporins
Number of aquaporins expressed on apical or basolateral surfaces of epithelial cells in various regions of renal tubules?
6
How is dilute urine produced?
Epithelial cells transport solutes but are impermeable to water…reduced expression of aquaporins = less water reabsorbed
How is concentrated urine produced?
Epithelial cells and surrounding interstitium are more salty than the tubular fluid, so high osmolarity of medullary interstitium allows urine to become concentrated as it flows through collecting duct
Osmolarity changes through a juxtamedullary nephron?
- Isosmotic fluid leaving proximal tubule becomes progressively more concetrated in descending limb 2. Removal of solutes in thick ascending limb creates hposmotic fluid 3. Permeability to water and solutes in collecting ducts is regulated by hormones 4. Urine osmolarityy depends on reabsoprtion in collecting duct
The clearance of a substance X is…
the volume of plasma cleared of X per time
If the clearance rate of X is less than the amount filtered, then…
X is being REASORBED by the nephron
The renal threshold fro glucose is 300 mg/100 mL plasma. Your cousin, a Type I diabetic, is having trouble regulating her sugar levels. Her plasma glucose is 400 mg/100mL plasma. What would be true regarding glomerular filtration of glucose and excretion of glucose?
It would all be filtered, but not all reabsorbed, so she would excrete glucose in her urine/
Effect of vasopressin on collecting duct?
Collecting duct is freely permeable to water, so urine becomes concentrated. Vasopressin is not there, tubule is not permeable to water, causing dilute urine.
Steps for aquaporin insertion into apical membrane casued by vasopressin?
- AVP binds to membrane receptor 2. Receptor activates cyclic AMP 2nd messenger system 3. AQP2 inserted into apical membrane 4. Water absorbed by osmosis into blood
What is membrane cycling?
Membrane vesicles containing aquaporin is added to plasma membrane by exocytosis and removed by endocytosis
What 2 things trigger release of vasopressin?
Increased plasma osmolarity and decreased blood volume/pressure
Why is it so important to regulate ECF osmolarity?
Affect cell size/volume = physical integrity of cells and tissues. Affects ionic strength = activity of macromolecules
Why does osmolarity fluctuate?
Variations in water intake/water loss and variations in Na+ intake/Na+ excretion
What are the consequences of osmotic perturbations?
Usually neurological. Hyperosmolarity causes seizures and death. Hyposmolarity causes headache/nausea/vomiting, leads to mental confusion, seizures, coma, death
Osmoreceptors?
Monitir plasma osmoloarity by increasing firing rate as osmolarity increases
Osmoreceptors are stimulated by?
Cell dehydration/shrinking
Where are peripheral osmoreceptors located?
Oropharyngeal cavity (back of mouth/throat) and within blood vessels that collect solutes absorbed from intestines.
What is the purpose of osmoreceptors?
Can detect osmotic strength of ingested materials and induce anticipatory responses. However, central osmoreceptors are the major points of regulation
Central osmoreceptors?
Cicumventricular organs (OVLT and subfornical organ) and supraoptic nucleus in hypothalamus (SON; origin of AVP-secreting neurons)
Secretion of AVP from hypothalamus?
1, AVP made and packaged in supraoptic nucleus of hypothalamus 2. Vesicles are transported down the cell 3. Vesicles containing AVP are stored in posterior pituitary 4. AVP is released into blood
Decrease in BP on the control of vasopressin secretion?
BP decreased, carotid and aortic baroreceptors decreae firing rate, sensory neuron send AP to hypothalamus, hypothalamic neurons synthesizeAVP
Decrease blood volume in the control of vasopressin secretion?
Decreased atrial stretch, sensory neuron to hypothalamus, supraoptic nucleus in hypothalamus makes AVP
Increased plasma osmolarity in the control of vasopressin secretion?
Hypothalamic osmoreceptors, interneurons to hypothalamus, supraoptic nuscleus makes AVP
Circadian rhythm in adults for AVP?
AVP increases at night so you conserve water and don’t have to get up to pee. First pee in the morning is super concentrated!
What creates the salt gradient in the renal medulla?
High osmolarity in the medullary interstitium…creates osmotic gradient for reabsoprtion of water
Why doesn;t osmolarity of ICF decrease as water is drawn out of tubules?
The anatomical arrangement of Loop of Henle and vasa recta are very close to one another, so it allows for the transfer of water and solutes between the two vessels. This is a COUNTERCURRENT EXCHANGE SYSTEM
How does the countercurrenct mutiplier work in the renal medulla?
The ascending limb transports ions, but not water into the interstitium, which causes it to become saltier and the filtrate to become more dilute. More salt moves into the vasa recta. The descending limb transports water but doesn’t transport ions, so water flows into vasa recta. This allows the interstitium to remain salty, allowing for concentrated urine to be produced.
Steps in ion transport in the thick ascending limb?
- 1200 mOsm entering ascending loop (hypersosmotic) 2. NKCC symporters on apical membrane reabsorbs salt via secondary active transport (moves Na+, K+, and 2 Cl-) K+ and Cl- leave basolateral side via co-transporters and Na+ leaves basolateral side via Na/K ATPase 3. Water cannot follow solute 4. 100 mOsm leaving ascending loop (hyposmotic)
Purpose of Loop of Henle?
- Pumping of Na+ and K+ in ascending limb is responsible for 25% Na+ and K+ reabsorption 2. Creates a salt gradient for the collecting duct that drive reabsoprtion of water in presence of AVP
If kidneys couldn’t clear any salt, what would happen to blood pressure?
There would be an increaed water intake (1.1 L), which would increase in ECF volume, which would raise blood pressure/
What is responsible for most of the Na excretion?
The kidneys. Loss via feces and sweating minimal under normal conditions (vomiting, diarrhea, and heavy sweating are the exceptions)
Is Cl- regulated?
NO. Na+ regulated, Cl- normally follws via electrochemical gradient via NKCC and NaCl symporters
Is sweat hyperosmotic or hyposmotic?
Hyposmotic, losing more water than salt
Homeostatic response to salt ingestion?
- Ingest NaCl 2. No change in volume, but increase in osmolarity 3. Vasopressin secreted, increaes renal water reabsorption and kidneys conserve water. 4. Thirst, increase water intake. 5. Increased renal water reabsorption and water intake causes an increase in ECF volume, which raises blood pressure and causes the kidneys to excrete more salt and water (slow response), which returns osmolarity to normal levels. 6. Increased blood pressure causes cardiovascular response to reflexively lower BP, volume and blood pressure to normal
Where is the only place Na+ reabsoprtion regulated?
The distal nephron. Unregulated in proximal tubule (always permeable to water) and ascending loop
Where is aldosterone synthesized?
Synthesized on demand in adrenal cortex and sent into bloodstream bound to carriers
Effects of aldosterone?
Rapid effects = modulation and existing pumps/channels Slow effects - drives transcription of genes with upstream aldosterone response elements, causing synthesis of new proteins and insertion of new pumps/channels
Target of aldosterone?
Principal cells (P cells) within epithelium of distal nephron
Steps in aldosterone response on P cells within epithelium of distal nephron?
- Aldosterone binds to cytoplasmic receptor 2. Hormone-receptor complex initiates transcription in the nucleus 3. Translation and protein synthesis makes new protein channels and pumps 4. Aldosterone-induced protens modulate existing channels and pumps 5. Result is increased Na+ reabsoprtion and K+ secretion
Stimulus for aldosterone secretion?
Increased plasma [K+] monitored by cells in the adrenal cortex (protects against hyperkalemia) 2. Decrease in BP
Primary action of aldosterone?
Na+ reabsorption and K+ secretion by increasing expression of channels (ENaC, ROMK), pumps (Na+/K+ ATPase)
Renin-Angiotensin System (RAS)?
- Angiotensinogen made in liver, circulates in plasma as an inactive precursor 2. Renin, secreted from granular cells in JGA of nephron, cleave angiotensinogen into angiotensis I 3. ACE (in endothelium of blood vessels) turns angiotensin I into angiotensin II 4. Ag II acts on adrenal cortex to synthesize aldosterone 5. Aldosterone works on principal cells in distal nephron
Cells that make renin?
Granular cells (JG cells)
What activates the RAS?
Low blood pressure and renin from kidney initiates pathway
How do granular cells of juxtaglomerular apparatus know when to release renin?
- Granular cells themselves monitor blood pressure in afferent arteriole, release renin i n response to decreased BP 2. Sympathetic neurons from cardio control centre in medulla terminate on JG cells, part of the baroreceptor response to dec. BP 3. Paracrine feedback from macula densa cells in distal tubule, decreased flow rate, leads to increased renin release (and vice versa)
Thirst can be stimulated by what 2 things?
Osmoreceptors shrinking and Ang II acting centrally on hypthalamus
KNOW HOMEOSTATIC RESPONSE TO DROP IN BP!!!
How ANG II affects arterioles, cardio control centre, hypothalamus, adreno-cortex
How is hypertension treated through the RAS?
Blocking Ang II…ACE inhibitors (cannot make Ang II), angiotensin receptor blockers, and direct renin inhibitors (no Ang I)
What is atrial natriuretic peptide?
A peptide hormone that is produced/released from specialized mycoardial cells mostly in the atria that is released when these atrial cells stretch more than normal. Acts to oppose RAS
Mechanism of natriuretic peptide?
- Acts on hypothalamus to decrease AVP 2. Acts on kidney to decrease Na+ reabsorption, increase GFR, and decrease renin, which increase Na+ and H2O secretion 3. Acts on adrenal cortex to decrease aldosterone 4. Acts on CCC to decrease sympathetic output
Main effect of natriuretic peptide?
Lowers BP
Why is the ECF concentration of K+ maintained in a narrow range, even though only 2% is found in the ECF?
It is a major determinant of resting membrane potential/excitability of excitable cells.
Hyperkalemia leads to what is regards to cell excitability?
Reduced concentration gradient, so K+ stays in cells = cell depolarizes
Hypokalemia leads to what changes in regards to cell excitability?
Greater concentration gradient, more K+ leaves cell = cell hyperpolarized (muscle weakness)
How is Na+ replaced?
Low Na+ triggers salt appetite, linked to ANG II and aldosterone (Na+ balance)
How is water replaced?
Thirst – controlled by centres in hypothalamus, respond to hyperosomolarity and ANG II
Although dehydration and hemorrhaging both involve a low volume alarm, how does the response to dehydration differ from hemorrhaging?
Dehydration involves loss of more water than solute, so there is also a hyperosmolarity alarm (do NOT need renin and aldosterone). Hemorrhage involves equal loss of water and salt, so no hyperosmolarity alarm.
Normal plasma pH?
7.38-7.42
Why is H+ concentration heavily regulated?
Affects tertiary structure of proteins, which is related to enzyme function. Abnormal pH affects the nervous system (acidosis = CNS depression and alkalosis = hyperexcitability/twitch). pH disturbances are also assocaited with K+ disturbances (partly due to renal transporter, H/K+-ATPase)
Where does the H+ input come from in the body?
Fatty acids, amino acids, metabolism, lactic acid, ketoacids
