Midterm 2- Renal Flashcards

(122 cards)

1
Q

What is the function of kidney?

A
  • removal of waste in urine, including urea, uric acid, creatinine (derived AA, nucleic acid, and creatine)
  • waste product filtered from blood by kidney and collected as urine
    1. Regulate Ionic composition of blood
  • ions in diff compositions within ECF and ICF
  • by affecting ion conc in blood, you are affecting ion conc in your whole body
    2. Regulate Blood Ph
  • protein in our body fold in a particualr way depending on Ph
    3. Regulate blood volume
  • kidney work with heart-> maintain blood volume
  • drink lots of fluid = inccrease blood volume which affects CV funcction
  • kidney detect volume via baroreceptors and volume receptors
    4. Regulate blood pressure
  • producing perfect amount of urine
    5. Maintain blood osmolarity- 300osmols
  • blood osmolarity -> total volume of fluid and all the solutes dissolved
  • change osmolarity by changing intake of solutes
    6. produce hormones
    7. Regualte blood glucise levels
  • kidney can maek glucose from toher sources if carbs are in depletion- gluceogenesis
    8. excrete wats and foreign substances
  • urea (AA), uric acid (nucleotide), crearine (creatin), urobilin (hemoglobin)
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2
Q

Describe the anatomy of Renal Physiology

A
  • two kidney bean
  • located posteriorly to abdomen (each side of spine at 11th and 12th rib)
  • outside the abdominal cavity
  • sandwichced between member that line abdoment and bones- called retroperitoneal
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3
Q

Draw the diagram of the kidney and name the structure

A

Renal vein- how blood exists the kidney
Ureter- urine travel out of this towards the bladder
Renal Artery- how blood gets into kidney
Cortex- looks granulated undder microscope
Medulla- pink stained layer
Renal pelvis- hallow space where urine is collected
Caylyces- collect urine from tissue segment (cortex and medulla) layer of kidney

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4
Q

Describe the supply of blood to the kidney

A
  • although kidney are small, it gets lots more blood relative to other organs based on its size
  • uses blood to metabolize, filter substances, etc
    Kidney: decrease Mass, increase blood flow
  • makes up less than 0.5% of mass but receves 20% of total cardiac output t
  • blood travels to kidney via left and right renal artery
  • blood is divided to provide blood to individual filtering units-> nephron
  • liver and kidney get most blood liver- filtering toxins
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5
Q

What are nephrons

A
  • each kidney has 1 million nephrons
  • made of two structures
  • Renal Corpuscle- function to filter blood
  • Tubule- processes the filtered fluid
  • afferent arteriole
  • provide blood supply to single nephron
  • part of nephron is in cortex and rest in medulla
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6
Q

What is renal corpuscle

A
  • receives blood via afferent arteriole
  • blood gets diltered into nephron and then called filterate (ultrafiltrate) which gets processed as it travels throughout rest of nephron
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7
Q

What is tubule?

A
  • tube structure of nephron
  • each part of tubule does something different to the filtrate thats moving through
  • Diastal tubule- much more twisted than proximal
  • both limbs of loop of Henle have a thick and thin segment
  • other nephron from other tubules join together on a contron collecting duct (usually 5 nephron share one collecting duct)
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8
Q

Draw the structure of the renal corpuscle with the tubule

A

see renal 1

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9
Q

Draw the diagram of the vasculature of nephron

A

Efferent arteriole- not all the blood that goes into nephron is able to be filtered sincce it is moving very quickly - how blood leaves corpuscle
Glomerulus- capillary bed inside corpuscle
Afferent arteriole- brings blood into corpuscle
Peritubular capillary- capillary bed surrounding the tbule section; function is to reabsorb from filterate

  1. Ascending loop of henle twists back and passes by the renal corpuscle
  2. blood vessel wrap arond the tubule component of nephron
  • unlike other structures, in the kidney, there is a capillary bed followed by another arteriole (NOT ventricle)
  • VDMs control constriction/dilation of afferent/efferent arterioles
  • portal system- series of capillaries and arterioles
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10
Q

What are the two types of nephron?

A

Cortical and Juxtamedullary nephron

- nephron based on anatomical distinct regions within kidney leading to variation in overall function

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11
Q

What are the differences between two types of nephrons

A
  • location of corpuscle within cortex
  • length of loop of hereles
  • origination of capillary beds that surround the tubule of cortical vs juxtamedullary nephrons
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12
Q

Where are the upper portion and lower portion of nephron

A

Upper portion- cortex
- has corpusclce which give the appearance of spots
Lower portion- medulla
- has loop of herles which give a straited look

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13
Q

What are the differences in nephrons?

A

Cortical= sits further to the surface of kidney within the cortex while JX corpuscle situated right beside medulla layer
Cortical has smaller loop of herle and more twisted peritubular capillary bed

JX

  • long loops of henle and orginization of blood vessel that contribute and maintain the increased osmolarity of the medulla ability of kidney
  • osmolarity increase of interstitial tissue is essential in our ability to concentrate urine
  • medulla osmolarity contributes to final urine volume
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14
Q

What is Vasa Recta? What is peritubulaary capillary

A

Vasal Recta- blood vessel that run parallel to juxtamedullary nephron
Peritubulary capillary- blood vessel that run parallel to cortical nephron

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15
Q

Describe the two structures in the renal corpuscle

A
  • renal corpuscle of every nephron is found in cortex of kidney
  • granular appearance
    Two structure:
    Bowmans capsule- fluid filled hollow ball-like structure that surrounds the glomerulus
  • capsule is continuous with the proximal tubule (beginning of first part of tubule)
  • made of epithelial cells (endothelial cell is type of epithelial cell)
    Glomerulus- specialized structure of leaky capillary
  • maded of endothelium
  • pores so large that everything smaller than red and white blood cell in blood can be filtered out
  • endothelium of glomerulus is fused with epithelium of bowmans capsule
  • by layer of extraceullar matrix0 basal lamina composed of collagen type 4 and negatively charged glycoprotein -> lack of fironectin found in basement
  • seres as rough sleve to further filter exclude nearly all plasma protein from entering bowmans capsule
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16
Q

Draw the diagram of the close up of renal corupscle with the function of each aprt

A

Bowmans capsule - outside part made of single layer of epithelial cells
- low metabolically active, very basic
Capsular space- does not modify filtrate, where the fluid filters into
Podocytes- part of the capsule that touch the glomerulus
- wraps around the glomerular capillary to prevent some of the fluid from filtering out
- components are continous with bowmans capsule
- fluid can move inbetween podocytes but not through
Proximal tubule- ability to modify fibrate
Endothelial cells of glomerular capillary
- jave special finger-like projections; leaky
Afferent arteriole- brings the blood in
Juxtaglomerular cells
- compose of part of the afferent arteriole
- respond to signals from maculla densa cells
Juxaglomerular apparatus
- helps control fuild filtration
Macula densa cells of ascending limb
- detect Na and Cl- chemoreceptors
- fluid composition and singal to Juxtaglomerualr cells that relase enzymes and cofactors to modify arterioles

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17
Q

What are podocytes

A
  • specialized epithelial cells surround the glomerulaar capillaries
  • long, foot like processes that interlace with each other and around glomulaar capillaries
  • connected to basal lamina
  • leave narrow slits around capillaries to control rate of fluid filtration into bowmans capsule

epithelial cells that make up the outside of capsule are continous with podocytes

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18
Q

What happens when there is adamage to podocytes?

A
  • increase in filtration of fluid

- role of podocytes in exclusion of proteins from entering bowmans space

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19
Q

Describe the barriers to filtration and how each component contributes to production of filtate

A
  • ions can flow through the pores in between endothelial cells of the capillary
    -slits between the podocytes allow solutes to flow through
  • basal lamina is a barrier to filtration (prevents proteins)
  • in order to get out of the blood and into capsular space, you have to pass inbetween the pores through the basal lamina and in between the podocytes
  • proteins- excluded by pores and basal lamina since proteins are negatively charged
  • small peptides will go through but they are negligible in conc
    does not allow RBC and WBC to pass through

Powerpoint version;

  • Blood filtered in the renal corpuscle is called the filtrate
  • Substance that shouldn’t be filtered will never make it in the urine in healthy individual
  • Substances that Shouldn’t be filtered in the capsular space: Proteins, Red blood cells, White blood cells because of the structure of the cor puscle
  • Gaps in between the cell that make up the glomerous- called endothelial cells in red
  • Components of the blood cannot go through the pores but in between the pores
  • Spaces between the podocytes- called slits cannot go through the podocytes but can do in between the slits
  • Podocytes which are modified epithelial cells are physically adhered to the capillary bed through the basal lamina
  • Basal lamina- made of collagen type 4, negatively charged glycoproteins and they re organized in layer, lacks fibronectin that is found in basement membrane (basal lamina and basement membrane are different)
  • Epithelial cells sit on basaement membrane
  • Glomerular tissues secrete basal lamina
  • Things go through the blood, they have to pass in between the pores
  • RBC and white blood cells are too big so they are excluded by the pores
  • Proteins come in variable sizes, as a whole, proteins have a negative charge, excluded by negative charge of basal lamina or size barrier by the pores
  • Small peptides that will go through – negligible in concentration

Filtered material
Plasma – made of water
Ions – Na, K, Cl,
Glucose
Amino acids – small
Podocytes – restrict the fluid flow – filter less fluid if the pores are close together and vice versa
How can the negative ions go through the basal lamina? Ions are so small but the gaps are big, the basal lamina doesn’t cause a big repulsion

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20
Q

Describe the basal lamina

A
  • extracellular tissue that adheres the glomerulus to podocytes
  • doesnt inhibit negative ions (both positive nad negative to go through )
  • hydrophillicc metabolites, water, glucose and AA go through
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21
Q
Why should Urinalysis be performed? Determine whether these sub should or shouldnt be present and why? 
Leu
Nitrite 
Urobilnogen
Protein
Ph
Haemoglobin
Specific Gravity
Keton
Bilrubin
GLucose
A

Overall health of the body can be quickly assessed by measuring components of urine.

Leu- WBC – bad, problem with barriers to the filtration, pores of the capillary are too big
Nitrite – bad- Nitrate (good) – have a bacterial infection, bacteria will metabolize nitrate and turn it into nitrite
Urobilinogen – in low conc its good, comes from bilirubin (hemoglobin), high conc , than its due to blockage in bile duct liver
Protein – bad because its too big, protein of urine causes frothing if there is problem with barriers in filtration, if we are ingesting too much protein
pH – 6 – a little acidic due to most of the foods are acidic, so it adds to the load of additional acid ;
Haemoglobin – bad (its protein( normally found within the blood cell, shouldn’t make it in the blood plasma if its in RBC, hemeolysis (RBC rupturing so hemeoglobin are being released and filtered), which isn’t good
Specific gravity – conc of the urine (solute composition), how many solutes and the mass of the solute, the higher the specific gravity, the more conc, the more dehydrated you are, you have less volume but still have solutes, different with osmolarity which doesn’t look at mass
Ketone – bad, when you have ketone, ketone gets produced by starvation, your body will break down lipids, triglycerides, the triglyceride will be produced into ketone and will be excreted in ketone, ketogenic diet, to treat things or load up on macronutrients
Bilirubin – bad because it is a product of liver (byproduct) passed through bile duct, if you have bilirubin, there is a probem with your liver or you have too much hemeoglobin by breaking it down
Glucose – bad, never gets excreted, tubule cells of the nephron, reabsorption of the glucose has the problem (100% reabsorbed)

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22
Q

What is the tubule anatomy

A

-sections of tubule have distinct function based on the cells that make up the structure
- tubule of nephron -> made of single layer of epithelial cells attached to a bbasement memerbaen
- cells have the ability to specfically transprot substancecs
tight junction protein seal the cells
- each section of tubule varies in the type of epithelial cellsand the level o f tightness in junctions

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23
Q

What are the three types of cells and describe them

A

Columnar- homogenous population of small cells
- faces isnide of the tubule (microvilli)
- proximal tubule cells
- contains microvilli to increase the SA for exchange
ATP depended process for the function of transporters so contain many mitocondria

Simple Squarous- metabolically less active

  • thin part of the descending and ascending loop
  • not as many mitococndria
  • important for reabsorbing substances from filtrate which don require a lot of energy
  • homogenous
  • function as a barrier, not leaky

Cuboidal- mixed population in collecting duct
- heterogenous population
both cell types are polarized
Principle cells - prodominant type, responseibe to hormones, metabolically active, reabsorb water and Na
Intercalated cells = less in numbers, balance acids and bases and have longer microvilli to max SA and effectively exchange even tho they are less in numbers

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24
Q

What happens if the podocyte slits are close together?

A
  • filter less fluid

- restrict the fluid flow

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25
What are the filtered materials?
Plasma Ions Glucose AA (small)
26
Describe the four processes of nephron
- kidney filter 180L of plasam/day - only excrete approx 1.5 L of urine / day - which means 178L was reabsorbed - 4 processes: Filtration: movment of solution from blood into corpuscle (only occurs in renal corpuscle of the nephron) Reabsorption: movement of items from tubule to surrounding vasculating (main) Secretion- movement of items from peritubular capillary into lumen of tubule - these are items that didnt have a chance to be filtered eg. penicillin, antibiotics NOT PROTIENS Excretion- anythhing that got left beind in the tubule will collect in the renal pelvis to be removed from body- it will not be processed further
27
What is glomerular filtration
- 20% of blood that enters the kidney is filtered into bowmans corpuscle - rate of fluid filtration is regualted to prevent filtering too much ro too little in nephron - Ultrafiltrate- fluid that filters into bowmans space *important to filter a large volume to achieve homeostasis
28
What is the consequence of filtering too much fluid into kidney
- problems balancing ions , dehydration, damage barriers to filtration - High BP = causes more fluid to be filtered, which would rupture glomerulus capillaries (ultimately lose number of nephron functioning - you can only repair tubular structure by local cells but cannot regenerate nephron
29
What is the consequence of filtering too little fluid into kidney
- results in back up of waste products | - cannot maintain homeostasis
30
What is the glomerular filtration rate
- amount of fluid that are filtered/unit into bormans space from glomerular capillaries - rate of filtration due to forces that exist in nephron - combination of forces called net filtration pressure
31
What are the four forces that contribute to net filtration pressure
1. Hydrostatic pressure of glomerular capillaries 2. hydrostatic pressure of bowmans capsule 3. Colloid osmotic pressure of glomerular capillaries 4. Colloid osmotic pressure of bowmans capsule
32
What is the effect of hydrostatic pressure of glomerular capillaries?
- pressure created due to presence and movement of blood through glomerular capillaries - leaky = good for filtration - increase filtration - largest fore that contributes to filtration PGC
33
What is the effect of hydrostatic pressure of bowmans capsule?
- pressure created due to presence of filtrate in bowmans space - takes time for fluid in capsular space to process through the tubule, which inhibits filtration - decrease filtration PBC
34
What is the effect of colloid osmotic pressure of glomerular capillaries
- pressure due to presence of protein in blood of glomerular capillary - protein exert an inhibitory force towards filtration and thats because they want to retain the water near them - decrease filtration piGC
35
What is the effect of colloid osmotic pressure of Bowmans space?
- pressure created due to presence of proteisn in the filtrate in bowmans spacec - if protein get into this capsular space = good for filtration - also bad because proteins shouldnt be there - increase filtration piBC
36
Write the equation of net filtration
PGC+piBC - [ PBC+piGC] Net filtration = 10mmHg If NFP calculated is greater than 10- more filtration If NFP is less than 10- less filtration
37
Draw the diagram for filtration and determine the largest force
PGC>piGC>PBC>piBC
38
What is filtration coefficient
- net filtration pressure (mostly contributes to GFR) + other factors also affect rate of filtration - filtration coefficient - how much SA (size of slits between podocytes) is available for filtration and the permeability of barriers to filtration (change in basal lamina ie remove the opportunity for protein to get out of blood)
39
What happens to GFR - glomerulaar filtration rate if: 1. increase space between podocytes 2. increase permeability of bsal lamina 3. increase size of glomeruli pores
1. Increase filtration 2. Increase filtration rate and fluid flow rate (thinner, destroyed mutation of glycogen, proteins will be filtered 3. decrease filtration rate
40
What are the two mechanism by which kidney protected from high pressure?
- the largest contributor to net filtration pressure is blood pressure experienced by the kidney 1. Myogenic response 2. Tubuloglomerular TG feedback - maintain GFR despite changes in BP -> filtration rate same when exercising and resting
41
What is the myogenic response?
1. BP increased 2. afferent arteriole stretches 3. stretch sensitive cation cahnnels open in smooth msucel of arteriole 4. smooth msucle celsl in afferent arteriole depolarize 5. VG calcium cahnnels open 6. smooth msucle contract - local vasoconstriction - reducing the diameter of afferent arteriole 7. BP and bloow flow decreases in glomerulus 8. GFR maintaianed Autoregulation maintains a nearly constant GFR when MAP is between 80-180mmHG - protective mechanism to inhibit the desruption of glomerulus capillaries
42
What is tubulogiomerualr feedback and describe the mechanism
- regulation of GFR locally by filtrate content 1. increase GFR due to increase BP 2. more water and ions are filtered into capsular space 3. Mucula densa cells (found at specialized junction) detect reise in NaCl therefore release a chemical messenger ATP which is cleaved extracellularly to adenosien 4. Adenosine causes vasoconstriction of afferernt artiole (alpha 1 receptor) 5. GFR decreases - adnosine is a vasodilator but in kidney, it is a vasoconstrictor (due to diff receptors) a2- vasodialte a1- vasoconstrict 1. decreasae GFR due to decreasae BP 2. less water and ions filtered into capsualr space 3. Mucular densa cells detect drop in Nacl and release NO 4. NO vasodialates afferent arteriole 5. increase GFR
43
How can you measure GFR?
- difficult to measure GFR because cannot measure the amount of fluid that filters into our nephrons without being invasive - explote info by measuring urine output Excretion (X) = Filtration (X) - Reabsorption (X) + Secretion (X) if substancce X isnt reabsorbed or secreted, rate of excretion = rate of filtration
44
Is measuring total urine produced in a day sufficient for determining how much fluid was produced in a day?
No! some filtered fluid may haave been reabsorbed and or secreted
45
What are the key characteristics of perfect substance to measure in a urine? and provide an example
- a substance that isnt reabrosbred or secreted - waste product is only filtered eg. creatinine - made from muscle breakdown - the rate at which this si excreted from body will give you the filtration rate - the rate at which the selected substance was cleared from body into urine becomes equivalent to how much substance was filtered
46
What is the equation of GFR?
GFR = [Substance X] urine * Urine Volume / [substane C] plasma - determines how much they should have filtered based on howm uch was in their blood
47
How do you calculate filter load? How can you determine renal handling
- how much of that solute is filtered into capsular space Filtered load of X = [x]plasma * GFR -once the filtered load was calcualted, cmeasure how much of the substancce X was excreted through urine analysis -> based on how much X was excreted, we can hypothesize renal handling of that substance
48
Calcualte the filter load of glucose if conc of glu is 1mg/ml of plasma. GFR = 125ml/min = 180L/day
Filter load = [G] * GFR = 1mg/ml * 125ml/min = 125mg/min sample the urine to determine how much glucose was excreted to hypothesize the renal handling health individual should have no glucose in urine
49
Draw the diagram of the overall tubule function
- cells of tubule express diff channels/transporters to move substances out of filtratie and into the blood - each segment has a diff job and diff volume of filtrate that it canreabsorb Proximal - 65% volume reabsorbed- Glu, AA, H2O, Na, K, Cl Descending loop of henle- water and minimal Na Ascending loop of henle- Na, K, Cl (no water reabsorbed due to lack of transporters) Loop of henle- 20% of volume Distal tubule- Na, K, CL- and Ca2+ Collecting duct- Na, H20- differential reabsorption- dependent on how much Na and water you injested to begin with - mostly affected by hormonal response Distal and collecting- 14% volume reabsorbed 2% volume excreted Renal 19
50
Draw the diagram of tubule transport
Renal 20
51
Define luminal, basolateral
Luminal- membrane portion of tubule cell that faces the inner lumen of tubule Basolateral- other side of the tubule cell membrane that faces the capillary is basement memebrane - also in close proximity to the capillary bed that surrounds the tubule and allows for efficient exchange of substanes in between the filtrate and the blood
52
What are two types of reabsorption
Reabsorption- movement from lumen to interstitial space Paracellular- movemetn between the tubular cells Transcellular- movement throug hthe vells via cahnnels in both luminal and basolateral membrenae - more common * when soemthing gets into interstitial space, ti will go to the capillary bed If the capillary was around cortical nephron, it would be peritubular capillary and if it was juxtamedullary, it would be vasa recta
53
What is the type of secretion
- very specific, controlled - generally transcellular - from blood, a transporter on basolaateral membreane allows the motion into the tubular epithelial cell and than another cahnnel on luminal memrbaen allows items to be secreted into lumen
54
What is a channel and transporter?
Channel- protein lined pore | Transporter- protein embedded in membrane
55
What is Na reabsorption?
- Na is the ion that drivesreabsorption throughout the tubule 30 times concentration grdient from filtrate to tubule cell - since filtrate in lumen is derived from blood pasma, it has a Na conc of 150mM - Na wants to leave the filtrate into the tubule cell - if there are ion cahnnels and transporters in the luminal memrbane, Na will move into tubule epithelial cells - there are also active transporter on basolateral memrbane that will move Na out of the tubule cell- maintian conc gradeint
56
What are the four types of Na resbsorption transporters?
1. Na Channel- ENaC - protein lined pore, Na+ passes either direction; favourabe motion of Na from filtrate into tubule 2. Na+ symporter- Na/Glu symporter- SGLT1 and SGLT2 - Na goes down its conc gradient transporting glucose with it, physical binding of Na and glucosse -Na and gluoc will move into cell - Symporter (moves only in one direction) SGLT1- 2Na+/1 glucose SGLT2 (major)- 1Na/1Glucose 3. Na+ exchanger- Na/H exchange- NHE3 - regulated by Ang2 (facilitated transporter that binds Na but moves Na inside the cell and H outside the cell to maintian the electrical gradient/exchange 4. Na/K ATPase - requires ATp since both items are moved against conc gradient - expressed in every tubule cell - position of transporter important - moves 3Na out and 2 K inside the cell
57
What are anion transport?
- reabsorption of ions must remain electroneutral - for every cation, an anion must be reabsorbed - major anion- Cl-; lesser extent -> bicarbonate - Blood (eg. of finite fluid volume) must have equl amounts of anions and cations Na is reabsorbed in the proximal tubule: - msot of the filtered bicarbnate is reabsorbed in proximal tubue - 60% of total chlorise is reabsorbed at proximal tubule and rest as the filtrate travels throughout the tubule - when we reabsorb Cl-, we have to make sure that the cell isnt depolarizing
58
What are the issues with Chloride transport?
1. trnasport into tubule cell (inside of the cell is negative) from the lumen is against electrical gradeint - so move Na first and than move Cl 2. transport out of tubule through the basolateral membrane must be high enough to move down a chemical gradient (outside of cell is high in Cl- so there isnt a chemical gradient available)
59
What are the exampels of Chloride transporter?
1. Cl- channel- Cl- protein lined moves in either direction (favourable) 2. Cl- symporter (NCC)- move Na and CL- in the same direction 3. Cl- multiporter NKCC2 (expressed in kidney)- moves many ions in the same direction)
60
What is water reabsorption?
- as osmolarity of filtrate decreases by movement of Na into tubule cells, water follows - unless there are transproters for water, it is unable to move by itself through cell memrbaen of epithelial cells - in some sections, water is able to move paracellularly - In other sections, water is unable to reabsorb paracellularly or transcellularly- impermeable to water - water always follows the direction of solute movement - as ions like Na and CL- are being reabsorbed in tubule epithelial cells, water would like to follow via osmosis - only do that if there is a transporter in the membrane
61
What are the examples of water transporters?
1. Water channels - Aqua 1,2,3,4 - Aqua 2 is functionally diff from rest- regulated by Ang 2 - simple diffusion - human genome encodes 4 diff water channels 2. Paracellular water reabsorption- occurs in proximal portion of the tubule and nowhere else
62
What are the types of transproters found in proximal, which ones are regulated by hormone and why?
Secondary active transport: Na+/Glu symporter -SGLT2 highly expressed - glu is not favourable because it is high in the cell - only part of the tubule for transporting glucose Na+/AA - 20 diff types present Na+/H+ exchanger - Na inside the cell and H outside the cell - maintian pH - bind with bicarboante to stabalize it because there isnt a transporter availabele for bicarbonate early on in the tubule - regulated by ANG2 Aqua 1 - favourable movement of water from tubule to inside of the cell as increase in solute inside the cell ``` Basolateral Primaary active transport Na/K ATPase - regualted by ANG2 maintian the electrochemical gradient ``` ``` Glu uniporter - favourable gradient AA uniporter - fav gradient Paracellualr reabsortpion of: K- down conc gradient Cl- outside/interstitial fluid is positively charged, chemical gradient H20- water follows ions osmosis ``` H20 Aqua - favourable movement
63
What is diabetes mellitus? what is osmotic diuresis
- urine should not contain glucose - when there is inccreased filtered load of glucose, the SGLT transporter become saturated because its a secondary active transport, takes time to transport glucose - increasaed glucose in filtrate causes water to follow inside the filtrate due to osmosis - increase urine volume
64
What are the renal and non-renal symptom of diabetes mellitus?
Renal- increase glucose and increase urine output Non-renal - ketoacidosis (production of glu from triglyceride andd fats as body thinks its starving itself as there is less glucose reabsorption
65
What are the types of transproters found in descending limb of henle, which ones are regulated by hormone and why?
Luminal and basolateral Aqua 1- water moves by osmosis - interstitial fluid of medulla is very high in osmolarity - further the loop of henle, the higher the osmolarity (set up high in embryonic stage) Luminal Na+ transport- ENac Basolateral Na/K AtPase - 3 na out for 2 K in - cells are metabolically active
66
What are the types of transproters found in ascending loop of henle, which ones are regulated by hormone and why?
- thick cells; more metabolically active Luminal 1-Na+ transporter 2- NKCC2 -transport Na, K and 2 Cl2 - Na is the favourable ion - CL is not because it is moving against electrical gradient - K is not because it is moving against conc gradient - moves three ions becayse it wants to keep everything electrically neural 3. K transporter -not a lot of K in the filtrate so for NKCC2 to keep functioning in the kidney, the K gets recycled back into the filtrate Basolateral 4. K+/Cl- symporter to move K and Cl in the same direction - K is favourable as it is high inside the cell 5. Cl- channel - It is negative inside the cell, thus Cl- moves favourablly - there is a built up of CL inside the cell sincce NKCC pumps 2 Cl inside, so you need to remove the excess Cl- buildup 6. Na/K pump 7. Movement of Na intacellularly - electrical gradient - build up of negative charge in the interstital to drive the Na+ in the interstitial fluid
67
What are the types of transproters found in distal convoluted tubule, which ones are regulated by hormone and why?
Luminal 1. Na channel 2. Na/Cl- symporter 3. Ca2+ reabsorption transcellularly Basolateral 4. Na/K ATPase 5. K/Cl- symporter (the same one that is present in ascending loop of henle) 6. Na/Ca antiporter - 3 Na inside for 1 calcium outside to interstitial fluid - Ca levels in body are important - ensure that we have adequate amounts of calcium - regulated by PTH
68
What are the types of transproters found in collecting duct, which ones are regulated by hormone and why?
Luminal 1. Na channel - ENaC - regulated by aldosterone 2. K+ - moves into the filtrate - regualted by aldosterone - K+ inside the cell can be dangerous 3. H20 Channel- Aqua 2 - regulated by ANG2 - channel an be endocytosis into the cytoplasm to inhibit reabsorption of water or present in the membrane Basolateral 4. Na/K ATpase - regualted by aldosterone 5. Aqua 3, 1 - not regulated by hormone
69
What is Gout and Kidney stones
- increased levels of uric acid (urate) in the blood is called hyperuricemoa (breakdown of purine AA) - Gout had kidney stones are caused by hyperuricemia - muct of the filtered uric acid is reabsorbed in proximal tubule (12 transporters ) due to its function as an antioxidant in the body - if in excess in blood, urin acid is secreted back into tubule - behaves as an antioxidant protecting the brain -secretion of uric acid is regualted so we do not have too much uric acid in blood Problem: - increased level in blood due to deficient secretion or increase formation can lead to kidney stones or gout
70
What are the causes of increasaed uric acid
- defect in transporter - secretion in transporter - reabsorbtion increase - dietary sources- high in purines; red meat, sea food, beer and wine
71
Describe gout and the symptoms of kidney stones
Gout- crystalization of increased urate or uric acid that deposite in joints Symptoms Gout; swelling and painful joints Kidney stone- crystals form stones in kidney; block in uric tract Symptomdecreased urine output, painful if stuck in ureter
72
What are the two systems to regualte body levels of sodium? When are they activated?
Renin is responsbiel for maintaining Na balance and can alter excretion in order to maintian homeostasis 1. Renin-Angiotension-Aldosterone System RAAS - gets activated when Na levels are low - produces two hormones and 1 enzyme 2. Atrial Natriuretic Peptide ANP - Na levels are hihg
73
What is the effect of Na on ECF and bloodd pressure ? what receptors in our body detect this change and activate which pathway?
- when Na levels arae high, the ECF volume increases and blood pressure increases as well - have receptors to detect changes in blood pressure and filtrate composition to activate these pathways - RAAS or ANP
74
What is the connection between Na levels and blood pressure?
- kidney also controsl osmolarity of ECF volume - if Na ions levels are high, ECF volume expands causing an increase in total blood volume - when blood volume is high, blood pressure is high as well - body uses mechanisms to detect changes in blood pressure as well as composition of filtrate to regualte Na content using baroreceptors Na levels in blood is closely linked to ECF volume- More Na ingested = more Na absorbed in GI tract = more H2O absorbed (retained) in body - the way our body determines whether Na is high or not
75
Describe and draw the RAAS Pathway
- Liver constitively produce ANG- 452 AA in size, no function - ANG is cleaved by renin that is produced by Juxtaglomerular cells (limiting factor) - renin is released when JX cells get specific stimuli for the production of ANG1 , whicch has no biological function - ANG1 binds with ACE enzyme that is embedded in the endothelial cells- highest expression in lungs as all the blood passes through the lungs after leaving the heart and ANG1 is converted to ANG2 - ANG has biological funcction - celsl in the adrenal cortex recognize ANG2 and produce aldosterone
76
What are the propoerties of ANG2?
- peptide hormone - stimulated by nenin release - vasoconstrictor - acts to increase Na reabsorption
77
How does ANG2 act in the tubule?
Proximal tubule 1. - increases activity of Na/H exchanger (small peptide so it is easily filtered in tubule) - increeases Na inside the cell 2. - increases activity of Na/K ATPase - increase Na in the interstital fluid Afferent arteriole - vasoconstrictor - both arteriole constrict to decrease GFR so flow of fluid rate is decreased to allow increase time for Na reabsorption
78
What are the properties of Aldosterone?
- steoid hormone - made by adrenal gland - stimualted by ang 2, high K levels and adrenal corticotropin hormone - increases Na reabsorption in collecting duct
79
What activates Aldosterone?
- ANG2 - high K levels - adrenal corticotropin hormone
80
What are the effects of aldosterone on the tubule?
- easily able to pass into the tubule cell 1. increase Na/K ATPase - increase Na in interstitial fluid 2. Increase Na and K channels in luminal - increase Na into tubule and K out o tubule 1 and 2 are fast non-genomicc responses 3. increase expression of Na channels and Na/K ATPase
81
What is the regulation of renin release?
- renin is released in response to low levels of Na in blood - rate limiitng step in RAAS pathways - also released in low blood pressure (situations like hemorrhage)
82
What are the two sensors that regulate renin release?
1. Baroreceptors I. - located in carotid sinus, special neural reflec directly on Juxtaglomerular cells- sympathetic innervation from carotid sinus that releases norepinephrine to release renin II. intrarenal baroreceptors- able to detect changes in local blood pressure (Afferent arteriole will stretch less due to decrease in blood pressure, thus release renin 2. Chemorecepotrs - Macula densa cells are chemoreceptors that will detect decrease conc of Na via NKCC multiporter, they think that there is decreased BP - relese prostaglandin that will release Renin
83
How do macula densa cells respond to low Na levels? What are the other things that the mucula densa cells respond to? What is controversial?
- contain chemoreceptors that detect decrease Na conc via NKCC multiporter - contain cilia that bend to response to filtrate flow rate - if NaCl content is low, it thinks that blood pressure is low as well Macula densa cells respond to - NaCl - fluid flow - BP 1. Release NO- vasodilator 2. GFR increasaes - dilate arteriole 1. release prostaglands 2. JX cells will release renin 3. renin will stimulate ANG2 which will cause the arterioles to constrict - GFR decrease - Since homronal response are globally, the GFR will decrease and constrict the arteriole to slow the blood flow and increase the time for Na reabsorption
84
what are the properties of Atrial natriuretic peptide?
- produced by atrial cells - peptide hormone - stimulus of high blood pressure - stretch receptors in atria detect increase in blood in atria
85
What are the two actions to reduce sodium reabroption by?
1. inhibit aldosterone release from the adrenal cortex | 2. increases GFR (ANP is a vasodialtor of the afferent arteirole)
86
What is the action of ANP and what three are the stimulus?
1. high Na, high ECF and high blood pressure 2. distension of cardiac atria 3. ANP is released 4a. Aldosterone release is inhibited 4b. vasodialtion of afferent arteriole 5. increase GFR (if fluid rate is increased, then it wouldnt have a chance to absorb Na+ ) 6b, 5a- increase Na excretion
87
What is the mechanism of Macula densa cells when there is high Na and high fluid flow rate?
- If there is high Na, than there is high BP, thus it wants preventative measures - releases ATP (cleaved to Adenosine extracellularly) - leads to vasodilator in other parts but vasoconstriction here - GFR decreased Constricts arteruoles - also blocks JG cells from releasing Renin - ATP and adnosine bind to JG cells via purinergic receptors to inhibit Renin Contradiction- ANP increases GFR by vasodilation of afferent arteriole in attemps to not give Na a chance to be reabsorbed - Global response so GFR Increases and there is DIALATION OF ARTERIOLE
88
How is water balance regulated in kidney?
- the volume of extracellular fluid is linked to blood pressure - when ECF volume is decreased due to a decrease in total body water, Anti-diuretic (Decrease urine production) hormone is released
89
Whaat are the properties of ADH?
- made by neuroendocrine cells in hypothalamus - stored in posterior pituitary - peptide hormone - triggered by release by low ECF volume, high plasma osmolarity and ANG2 - not enough water in blood, you have higher solute so high osmolarity and increasae production of ANG2 - sensed by baaroreceptors and osmoreceptors
90
What happens when there is increase or decreased ADH?
Increase ADH- binds basolateral part of collecting duct on Aqua 2 to increase water reabsorption Decrease ADH- no water reabsorption, endocytosis of Aqua 2 in cytosol
91
How is the water balance regualated by baroreceptors and osmoreceptors?
Baroreceptors - found in aortic arch and carotid sinus - also volume receptors in atria - when blood pressure and volume decreased, less action potential sent to hypothalamus, ADH released Osmoreceptors - located in and around the hypothalamus - an increase in plasma osmolarity causes osmoreceptors to decrease in volme, ADH released
92
How does ADH act on collecting duct?
- Once ADH binds on basolateral memrbane, the signal cascade causes water channels in vesicle in cytosol to be inserted in luminal membrene to increase water reabsorption - ADH is high, ECF is low, so you want to conserve water so increase water intake into the cell
93
What hormone balances water and what is the property?
ADH is the only hormone that balances water | - ADH has a short life span so in order to reabsorb water, ADH needs tp be constantly reelased
94
What happens when you do not drink any water and your osmolarity increases
- osmoreceptors in hypothalamus will detect the increased osmolarity - there will be increased activity of neuroendocrine cells (high solute conc will cause shiverling of the cell body located in hypothalamus, leading to increased AP in pituitary gland) - ADH gets increased in posterior pituitary - ADH acts on the receptors of colelcting duct- they increase aqua porin 2 channels in luminal memrbaen so more water is reabsorbed and less is excreted - this causes the conservatio nof body of water - there will be a negative feedback loop to osmolarity very depleted water will also stimulate the thirst center
95
What happens when there is decreased blodo volume due to dehydration and decrease MAP?
- blood pressure and decreased MAP will be detected by baroreceptors which will send less AP to solitary track nucleus and release the inhibiton and activate the hypothalamus - there would be increased secretion of ADH and release of ADH from psoteriod pituitary - ADH will act on the collecting duct of the kidney to increasse water reabsorption and decrease water excretion to conserve energy - there will be a negative feedback loop to the blodo volume receptors
96
How is there max ADH secretion?
- Increase in osmolarity and decrease in baroreceptors (volume and pressure) leads to maximal ADH secretion - ADH lives in plasam for few mins so you need constant input
97
What happened if there was opposed osmorecpetor and baroreceptor singal to ADH?
- Osmolarity during normal physiological is the main concern | - if there is increased osmolarity, and the volume was opposite, you would make ADH
98
What would be activated in times of hemorrhage?
Blood volume is drastically decreased, thats when baroreceptors take over and produce ADH - most ADH released than in any other scenario
99
Draw the diagram and Describe the filtrate osmolarity changes throughout the JX tubule
-Tubule of the JX nephron due to long loop of henle -Upper portion that has interstitial conc of 300 sit in the cortex -Deeper in the medulla, the conc of the interstation gets 1400 osmols -Function of development- as kidneys were forming, you already have a high conc medulla -The most conc part of the medulla will directly conc the max urine conc that you can produce -Blood that you filtered, filtrate has the same osmolarity as your blood- proteins, RBC and WBC cannot filter – isosmotic -As filtrate travels, glucose, AA, K, Na, Ca, Water, Cl, as solutes are being reabroed by Na, water follows by osmoriss through the proximal tubules, its permeable to water luminal and basolateral membrane -As filtrate travels, the conc at the end of the proximal tubule is 300 osmol, equal amount of solte and water is being reabrobed, the volume has decreased in the filtrate -As we descend down the loop of henle, the primary thing reabsorbed is water and little bit of sodium, thus the osmolarity will increase -Water moves becaue the medulla is conc -The conc at the bottom of loop of henle will havea filtrate conc of 1400 mOsm depending on how long the loop is as high as the outside interstitium -Ascending limb, absorbs ions to the interstitial spacec but not water -> impermeable to water – the conc of the filtrate is going to decrease- diluting segment of the nephrons, ions are reabored without water -The conc of the fitate , electorchemical gradient, conc gradient and paracellular transport Na in the ascending limb, so its not simple to say they are the same osmolarity, it ends up being 200mOsm diff than the outside fo the tubule, if the interstitial is 600 osmoles, the inside of the tubule is 400 osmoles, there is electrical gradient and paracellular leak that seems to be greatest differential that the pumps can work against -Distal convulated ubue- its similar to ascending tubule, it reabroebs ions but not water, the conc inside the tubule is going to be 100, the greatest diff is 200, thus the most diluted conc will be 300-200 = 100 -Asa the filtarate goes down the collecting duct, you get reabrobetion of ions and water -Lets talk about water and no ions -As filtrate goes odwn tof the collecting, if there is no ADH present, water is not reabsorbed, the collecting duct will be impermeable to water, the conc of the filtrate will be 100- sneaorio of drinking pure water, repress ADH reelased -If you had ltos of ADH, you will make the collecting duct permeable to water, the max ADH , you will have maximal water reabrobption, so that the conc of the urine will be as conc as the interstitial, it will be 14000mOsmoles Urine osmolarity will depend on reabsorption There are drugs that can change the osmolality of the interstitium, the ability t oproduce
100
What is diuresis, natriuresis. What is water?
diuresis - increasaed procution of urine natriuresis - increased excretion of sodium - water is a diuresis
101
What are three examples of diuretic and what do they do?
1. alcholo- inhibits release of ADH- produce mroe urine than you should 2. AVP receptor antagonist- ligand is ADH (like you have low ADH, produce high volume of urine) - leads to high blood pressure, conjustive hearth failute 3. NKCC transporter antagonist- decreases renal medulla osmolarity - derease Na reabsorption, so you affect osmolaarity of medulla - filtrate would end up haing high conco, so water will follow filtrate, leading to increase volume in urine
102
What is Diabetes insipidus? what would you classify as being neurogenic vs nephrogenic
- failure to release ADH - neurogenic or failure of collecting duct cells to response to ADH nephrogenic
103
Is caffeine dieuretic? does it affect ADH?
- affects heart rate, blood pressure, adnosine receptors cahnges the blood pressure by increasing it - blood pressure changes leads to increased urine output so you have autoregualtion of GFR - Caffeine does not affect ADH reelase
104
What is the difference between diabetes mellitus and diabetes insipidus?
Diabetes mellitus - increase urine production resutls from osmotic diuresis - diabetes insipidus affects the ability of ADH to stimulate water reabsorption in the colelcting duct of nephron - causes severe dehydration
105
What is the treatment of diabetes insipidus
- increase fluid intake
106
What happens to osmolarity and volume whe n you: 1. drink large amoutns of water 2. Injestion of isotonic saline 3. ingestion of hypertonic saline 4. dehydration (sweat loss, diarrhea)
1. increase voluem and decrease osmolarity- NO ADH release 2. No change in osmolarity and increase volume- INCREASE ADH reelase 3. INCREASE ADH release - increase volume and increase Osmolarity 4. ADH release maximally sweat is hypotonicc - decrease volume and increase osmolarity
107
Describe your bodys response to severe weating?
- body loses ECF fluid volume but sweat is hypotonic in comparison to body fluids, the osmolarity of plasma inccreases - when ECF volume decreases, one response of body is to release ADH due to activation of volume receptor - ADH functions to increase water reabsorption to prevent more fluid volume loss - inaddition, ECF volume decrease also triggers RAAS activation through the stimulation of baroreceptors - both ANg2 and aldosterone function to increase Na reabsorption, which aid in the osmotic reabsorption of water in tubule
108
Describe stamically how increaing plasma osmolarity and decreasing volume due to sweating
sweating - removal of hyposmotic solution 1. increase plasma osmolarity 2. ADH released 3. Increased water reabsorption 1. Decreased ECF 2. RAAS activation - a little renin is reelased because need three inputs to reelase lots of renin - medula densa cells do not release Renin 3. ANG2 and aldosterone 4. increased Na reabsorption - body is trying to conserve Na even though there is high plasma osmolarity - once you have normal ECF, you lose RAAS and ADH release from ECF - you will reabsorb water but not as much
109
What is the mechanism that kidney uses to perform acid/base balance?
- one of the important functionso f the kidney is regulation of pH - if extracellular fluid becomes too acidic, the kidney will remove H+ and conserve bicarbonate ions (HCO3-), which acts like a buffer - slower than lungs in regualting pH 1. excrete excess HCO3- or H+ 2. Reabsorb filtered HCO3- 3. Create new HCO3-
110
What are some of the sources of acids and bases in body?
Acid: 1. food- acidic fruits, amino acids that contain sulfure, fatty acids, etc 2. Metabolic intermediates- pyruvate, components of the citric acid cycle, lactate 3. lactic acid created by anerobic metabolism - when oxygen is depleted, you convert glucose into lactic acid 4. production of CO2 by aerobic respiration - CO2 acts as a weak acid in body- body has to deal with this everyday - CO2 combines with water to produce carbonic acid that dissociates into hydrogen ion and a bicarbonate ion - biggest source of acid in body Bases - foods- some fruits and vegetables metabolism to HCO3-
111
What is the equation for carbonic anhydrase? What happens when you add protons?
CO2 + H20 H+ + HCo3- | - the equation shifts left and produce more CO2 and water
112
What is the renal handling of bicarbonate in the proximal tubule
- reabsorbs most of the filtered bicarboante - the tubule epithelial cells cannot directly reabsorb bicarbonate; it must be first converted to CO2 - CO2 can directly enter the tubule by simple diffusion - once in tubule, it CO2 reacts with water to create hydrogen ions H+ and a bicarbonate ion HCO3 - a channel in basolateral membrane then reabsorbs HCO3- while the H+ is excretd into the lumen via the Na+/H+ exchanger
113
Draw the diagram for renal handling of Bicarbonate reabsorption in proximal tubule
- bicarbonate gets easily filtered in tubule (capsular space) however, there is no transproter on the luminal memrbaen of proximal tubule so it cannot be reabsorbed 1. NH3 secretes H+ in tubule in exchange for Na inside the tubule cell 2. HCO3- combines with secreted H to form CO2 and H2O due to the presence of carbonic anhydrase CA - proximal tubule have CA embedded in proximal tubule membrane - proximal tubule also has microvili for increase transporter 3. CO2 is a non-polar moledule that diffuses into cell 4. Co2 combines with water to form H+ and HCO- with the help of CA enzyme (cytosolic enzyme) - proton and bicarbonate is produced intracellularly 5. Proton is recycled back by Na/H exchanger - proton contributes to bicarbonate reabsorption 6. Bicarbonate and H symporter - bicarbonate is the favourable molecule that does not require ATP - Na is not favourable - Electroneural transport- negative molecule moved with positive ion to maintain neutrality of trnasporter - it is inappropraite to say that all Na protein carriers are always favourable 7. Na and bicarboante move into interstital space
114
Describe the role of collecting duct in hydrogen ion excretion
- collecting duct is region for fine-tuning of bodies pH - epithelial tubule cells of collecting duct will either secrete H ions or bicarbonate to balance the need in the body - to do this, bicarbonate must be converted to CO2 in lumen (like process in proximal tubule) - CO2 can freely diffuse into collecting duct cell and combine with water, a process catalyzed by enzyme carbonicc anhydrase, to form bicarbonate ion and a hydrogen ion - depending on pH of body, either a bicarbonate ion will be secreted into lumen or a hydrogen ion Too acidic - more hydrogen ion must be excreted - subtype of collecting duct cells use H+ ATPase to excrete the H+ into lumen, as well as H+/K+ ATpase antipor, both found in luminal memrbane - both require energy - an HCO3/CL- antiporter is located on basolateral memebraen to reabsorb the HCO3- into the blood stream
115
What is the mechanism in the collecting duct type A intercalated cell- response to acidosis
Type A and B cells - cells that respond to decrease in pH, increase H+ - Type A must become activated to do the job - function in presence of CO2 and water If there is acidosis and activation of Type A: - excrete the extra proton in urine via primary active transport (H+ATPase) or in exchange for K+ (H+/K+ATPase antiport) High H+ in blood stream : 1. H+ combines with bicarbonate in presence of CA to produce CO2 2. CO2 easily difuses into the collecting duct cells Starting 3. Co2 combines with water in presence of Ca to produce H and HCO3- 4. H+ will be secreted by (primary active transport): a. H+ATPase b. H outside and K+ inside ATPase because it goes through conc gradient for K - both transporters are present on luminal memebrane when cell is activated 5. The bicarbonate produced inside the collecting duct cell will go in the interstitial psace in exchange for Cl inside the cell - doesn't reqire ATP- keep it electroneural - HCO3- acts as a buffer to keep H+ conc small 6. Increased K inside the cell due to the H/K atpase is determental so there must be reabsorption of K inside the interstital cell- leads to increase blood K levels in plasma - leak out of K into interstitial due to K leak channel in basolateral memrbane 6. The bicarbonate wil combine with H+ with help of Ca that is embedded in the basolateral memrbane of Typa A cell , producing the Co2 that started the process -
116
What is the consequence of acidosis
- increased blood K concentration; hyperglycemia due to Type A cell and the way their proteins move ions
117
How do the Type A cell get activated?
- protons bind to proteins and change protein conformation - proton detecting proteins in the basolateral memebrane of Type A cell- pH sensor - cause activation of GPCR- intracellular signalling - move the vessicle which are cytosolic which contain H/K ATPase and HATPAse and inserting the vesiccles in memebrane putting the carriers in the luminal membrane allowing for proton to be secreted
118
What if the blood pH is too basic? What is the method of bicarbonate excretion in collecting duct Type B
- more bicarboante ions must be excreted - subtype of cells in collecting duct will have HCO3-/Cl- antiport on luminal memrbane to excrete HCO3- into lumen - on the basoalteral memebrane, H+ is reabsorbed into blood stream through the avtivity of an H+ATPase and H+/K+ATPase antiport
119
Describe the mechanism of bicarbonate (alkalosis) excretion in collecting duct Type B cells
- water and carbon dioxide are forming bicarboante and proton in presence of CA 2. HCO3- is secreted into filtrate in exchange for chloride into the cell 3. HCO3- is excreted in urine 4. Proton that is produced moves in baasolateral memebrane via H+ATPase or H+/K+ Atpase - H into interstitial space to brign the pH down - increased K inside the cell will be removed via K channels in luminal memebrane into filtrate
120
What is the conseqeunce of Alkalosis
- secrete K , become hypoglycemic decrease K in the blood
121
How are the Type B cells activated?
- decreasae in number of protons - proteins that sense the high pH another GPCR activated causing signalling cascade - vessicle mobiliation contain the bicarboante CL - antiporter - effecient secretion of bicarbonate - activated by LAC proton- indicates that pH has increased
122
What are the four causes of acid/base disturbances
1. Metabolic acidosis - excessive breakdown of fats/amino acids, ingestion of asprin, methanol and antifreeze 2. Respiratory acidosis - body doesnt get enough air (hypoventilation) - drug induced respiratory depression - airway resistance due to asthma - fibrosis - muscle weakness from muscular dystrophy 3. Metabolic alklosis - excessive loss of H+ due to vomiting - excessive ingestion of antacids 4. Respiratory lkosis - excessive amounts of CO2 exhaled (hyperventilation)