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What are the functions of the Kidney?
Remove waste products from the body
Maintain acid-base and water-salt balance
Regulate BP
Promote production of RBCs
Activate Vitamin D
MAINTAIN HOMESTATIS
What percent of cardiac output is done in the kidneys?
20%
What percent of ATP goes to the kidneys?
15%
How many times do you filter your entire plasma volume?
60 times a day
What are the processes of nephron?
Filtration
Reabsorption
Secretion
Excretion
STUDY ANATOMY
!!!!!
What is the path of blood through a nephron?
Artery
Afferent Arteriole
Golmerulus
Efferent Arteriole
Pertubular Capillaries
Vasa recta
veinV
Blood only filters what from plasma?
H2O, glucose, ions
What is the path of fluid (Filtrate) Through a nephron?
Blood
Bowman’s Capsule
Proximal Tubule
Descending limb of LH
Ascending limb of LH
Distal Tubule
Collecting Tubule
Collecting Duct
Processes of the Nephron: Filtration
From the glomerulus blood to the tubules, non-selective
Only size matters (coffee filter)
Processes of the Nephron: Reabsorption
Movement of solutes and water from lumen of tubules back into plasma
After filtration back to blood vessels. Is selective: requires channel from filtrate back into blood
Processes of the Nephron: Secretion
From Peritubular capillary blood to tubules, selective
Requires channel from blood into filtration
Processes of the Nephron: Excretion
From tubules to outside the body (urine)
The amount of substance X that is excreted in Joe’s urine increases. If the amount of the substance that was filtered did not change, what caused this increase?
If F is constant and E went up, either less of substance X was reabsorbed or more was secreted
Substance Y cannot be reabsorbed or secreted. If the amount of substance Y in the urine increases, what must have happened?
R and S are 0 so the only way to increase E is to increase F (E= F- R + S)
What are the three types of cells involved in Filtration?
Podocytes
Mesangial Cells
Endotheial cells
In Filtration: Podocytes
Wrap around glomerular capillaries, forming the filter through which plasma must pass.
In Filtration: Mesangial Cells
Support the glomerular capillaries and regulate blood flow through them
Filtrate must pass through what 3 layers?
Layers of Glomerular membrane
What are the layers of the glomerular membrane?
Capillary Endothelial cell
Basement membrane
Epithelial cell (podocyte)
Glomerular Filtration rate (GFR)
Amount of plasma filtered per unit time
GFR is determined by what?
Glomerular filtration pressure
Glomerular filtration pressure (GFP)
Driving force for filtration and is the sum of starling forces (pushing/pulling)
GFP Starling Forces
Pulling forces: Hydrostatic Pressure
Pushing Forces: Osmotic pressure
Under normal circumstances Pgc hydrostatic pressure created by BP is
The largest force contributing to GFP and thus GFR
If the efferent arteriole from the glomerulus is constricted, what happens to glomerular filtration pressure? Why? What happens to the glomerular filtration rate?
Constriction of the efferent arteriole will increase resistance and therefore increase GFP. Increased GFP will cause increased GFR
Steve’s blood albumin levels drop suddenly, what happens to GFR? Why?
Albumin is a large molecule that cannot cross capillary walls. It is a critical determinant of glomerular capillary osmotic pressure, which acts to reduce GFP. Reduced blood albumin would therefore reduce GFP, leading to increased GFP and GFR
Excretion is =
Filtration- Reabsorption + Secretion
Within the zone of auto-regulation: There are 3 mechanisms, of intrinsic control:
Myogenic Regulation
Tubulogomerular Feedback
Mesangial Cell Contraction
GFR is constant across a range of BP. How?
Zone of autoregulation: When GFR hit normal mean BP stays at that stop while increasing mean arterial BP
Kidneys keep BP regulated
Myogenic Regulation
Smooth muscle of the afferent arteriole contracts when it is stretched
Originating from muscle
Smooth muscle limits the amount of blood going in
Increased mean arterial pressure stretches the afferent arteriole, causing it to constrict
Tubuloglomerular Feedback
Macula densa cells release adenosine and ATP in response to increased flow
Tubules interacting with glomerulus
Cells sense changes in fluid flow
Mesangial Cell contraction
contract in response to stretching, decreasing the SA for Filtration
Decreases amount of filtration occuring
Explain the process of myogenic regulation in intrinsic control of GFR
Increase MAP
Increase Smooth muscle contraction
Increase resistance
Decrease blood flow
decrease Pgc
decrease GDP
Decrease GFR
Explain the processes of Tubuloglomerular Feedback in intrinsic control of GFR
Macula Densa cells sense increase in fluid flow by NACI
Secrete adenosin/ ATP
Increase contraction of smooth muscle
Increase resistance
Decrease blood flow
decrease Pgc
decrease GDP
Decrease GFR
Describe the process of Mesangial cells in intrinsic control of GFR
Increased mean arterial pressure in glomerular capillaries
Stretch of mesangial cells
Causes them to contract
Decreasing filtration surface area
GFR decreases
Outside the zone of auto-regulation, GFR is controlled extrinsically how?
TPR includes the kidney
Resistence in kidney capillaries
Sympathetic innervation
Decrease GFR
Decrease fluid loss
increase MAP
Extrinsic control of GFR
In response to an acute severe change in blood volume, GFR is reduced, conserving water
Baroreceptors detect decreased MAP and trigger renal sympathetic activity
Intrinsic control
Keeps GFR constance across a broad range of BP
Clinical implications of GFR
Filtered load
Clearance
Renal Plasma flow
Filtered Load
How much a particular solute is filtered per unit time.
FL= GFR x [x] plasma
Clearance
Volume of plasma cleared of a substance per unit time
Clearance= (concentration of x in urine) (Rate of urine production)/ concentration of X in plasma
Para- aminohippuric acid (PAH)
freely filtered, not reabsorbed. Any that is not filtered gets completely secreted
Inulin
Freely filtered and neither reabsorbed or secreted. clearance of inulin equals GFR
Creatinine
Occurs naturally in the body, freely filtered and only secreted in small amounts
Where does most reabsorption take place?
Proximal Tubules: Most
Distal Tubules: Fine tuning
In Reabsorption, what are the main barriers of movement?
Apical membranes
Basolateral Membranes
Of the tubular epithelium
What are the three types of reabsoprtion form filtrate back to blood?
Active solute transport
Passive water movement
Passive solute movement
In reabsorption: Active Solute Transport
Transporters can be on apical (x) or basolateral membrane (y)
Requires ATP and transporters
In reabsorption: Passive water movement
Transport of X and y increases plasma osmolarity so water follows (osmosis)
In reabsorption: Passive solute movement
Tubular concentration of solute Z is higher so it moved to the plasma (Often following water)
Down concentration gradient
What is the key for movement for solutes in the kidney?
Na+
Much of the energy used by the kidneys is for?
Na+/ K+ pump
What happens when the Kidneys capacity to reabsorb a substance is exceeded? GRAPH
The substance gets secreted because all transporters are used up (transport max)
Renal Threshold
Plasma concentration (glucose: example) when a substance is first detectible in urine
Diabetes Mellitus
Due to a deficiency in either secretion or response to insulin, glucose is not moved out of the blood and into cells
How do kidneys keep water?
Most of your body water comes in through food and drink
Most of your body water goes out in urine
Normally, fluid in = fluid out (Normovolemia)
What happens when fluid in does not equal fluid out?
Hypovolemia
Hypervolemia
Hypovolemia
(To little water in)
decreased plasma volume and results when water loss exceeds water gain
Hypervolemia
(Too much water in)
Increased plasma volume and results when water gain exceeds water loss
What are the consequences of hypovolemia and hypervolemia?
Changes in plasma volume directly affect MAP
Changes in plasma volume change osmolarity, affecting cells of the body
How do your kidneys change urine concetration?
By changing the permeability of the collecting duct
Increase aquaporins
concentrated urine
Reabsorb water
Decrease aquaporins
Diluted urine
excrete water
Kidney maintenance of fluid balance:
Diuresis
Antidiuresis
Diuresis
Excreting excess water (diluted urine)
Antidiuresis
conserving water, water back into plasma (Concentrated urine)
How is the kidney maintene fluid balance?
Changing permeability by altering number of aquaporins
How do your kidneys change urine concentration : Permeable membrane
Water flows out of the filtrate (concentrating the urine)
Antidiuresis
Response to hypovolemia
Lots of aquaporins
How do your kidneys change urine concentration: Impermeable membrane
dilute urine (diuresis
Response to hypervolemia
How do you change the number of aquaporins?
Circulating vasopressin binds to its receptor triggering a G-protein signaling cascade leading to the insertion of aquaporin 2 channels on the apical membrane,
How do you change the permeability of the collecting duct?
Regulating ADH
Low circulating ADH
Fewer aquaporins = reduced permeability= diuresis= dilute urine= removal of excess
High circulating ADH
more aquaporins= increased permeability= antidiuresis= concentrated urine= water saved
How is ADH regulated?
Posterior pituitary release ADH which up-regulates aquaporins, increasing urine concentration
Diabetes insipidus
Characterized by excessive urine and thirst.
Four types
Neurogenic
Nephrogenic
dispogenic
Gestational
diabetes insipidus: Neurogenic
Defect in the pituitary or hypothalmus- little production of ADH
Diabetes Insipidus: Nephrogenic
Defect in the kidneys’ response to ADH
Diabetes Insipidus: Dipsogenic
Damage to hypothalamic thirst center
Diabetes insipidus: Gestational
Overproduction of vasopressinase by mom
How does your body maintain Na+ homeostasis?
Regulating reabsorption
Na+ is freely filtered at the glomerulus and it is not secreted
How is Na+ reabsorbed?
Na+ / K+ pump moves Na+ out of cell into ECF
Na+ from tubular fluid moves down its concentration gradient into cell
How is Na+ reabsoprtion regulated?
By aldosterone
Increases the number of Na+ and K+ channels
Stimulates synthesis of Na+ and K+ pumps into basolateral membrane
More aldosterone =
More Na+ reabsorption and more K+ Secretion
How is aldosterone regulated?
Macula densa cells release adenosine in response to low Na+ in the distal tubule
This signal triggers granular cells to relase renin
Increased renin=
Increased aldosterone
The renin- angiotensin- Aldosterone System
Liver secretes angiotensiongen
Juxtaglomerular cells secrete renin which cleaves Angiotensignogen to Angionteniogen 1
Capillary endothelial cells secrete angiotension-converting enzyme which cleaves angiotensin 1 to angiotesin 2
Angiotensin 2 stimulates adrenal cortex to secrete aldosterone
Explain K+ homeostats
K+ is both reabsorbed and secreted in the nephron
K+ levels are regulated by secretion
Aldosterone has opposite effects on Na+ and K+
Increased aldosterone=
More Na+ reabsorption
More K+ secretion
Regarding Kidney Function
a. The clearaInce of glucose exceeds that of PAH
b. HCO3- is secreted
c. inulin is secreted
d. PAH is secreted
e. The clearance of inulin exceeds that of PAH
a. NO: plasma is completely cleared of PAH and glucose is reabsorbed
b. NO: Reabsorbed for bicarbonate
c. NO: Secreted or reabsorbed
d. YES
e. NO
Which one of the following statements about water reabsorption in the kidney is FALSE?
a. It takes place mainly in the proximal tubules
b. An increase in vasopressin will increase reabsorption
c. An increase in aldosterone will decrease water reabsorption
d. It depends on the proper functioning of the loops of Henle.
c. An increase in aldosterone will increase water absorption
Substances which are excreted at a higher rate than they are filtered include
a. inulin
b. glucose
c. PAH
d. Water
a. NO: Only filtered ( F=E)
b. NO: Filtered and reabsorbed (E=F-R)
c. YES: Excretion= Secretion + filtration (Completely cleared)
d. NO: filtered + reabsorbed (E= FML- R)
A person’s urine is tested and found to contain glucose. This person could have all the following except:
a. diabetes mellitus
b. Diabetes Insipidus
c. A filtered load of glucose greater than the Tmax for glucose reabsoprtion
d. A plasma glucose concentration greater than the renal threshold for glucose
B. Diluted urine