Pathophysiology Exam #4 Flashcards
What are the ten functions of the Renal System?
REVIEW OF KIDNEY FUNCTIONS
• EXCRETE END PRODUCTS OF METABOLISM FROM THE BLOOD, such as urea, creatinine, metabolic acids, others
• In coordination with antidiuretic hormone (ADH), REGULATE VASCULAR, INTERSTITIAL, AND INTRACELLULAR OSMOLALITY
AND VOLUME by regulating urine volume and osmolality
• REGULATE ELECTROLYTE AND OTHER SOLUTE BALANCE of body fluids
• REGULATE ACID-BASE BALANCE OF BODY FLUIDS, in conjunction with body buffers in the lungs
• REGULATE BLOOD PRESSURE by controlling vascular volume and by secreting renin, which causes synthesis of
angiotensin II (potent vasoconstrictor) and aldosterone secretion and the lungs
• REGULATE BONE MARROW PRODUCTION OF RBCS BY secreting erythropoietin (from the peritubular endothelial
cells) in response to hypoxia
• SYNTHESIZE VITAMIN D TO it’s most active form, 1,25-DHCC, which helps regulate calcium and phosphate
balance and bone formation
• SYNTHESIZE VARIOUS HORMONES that help regulate renal blood flow, such as PGs (prostaglandins, which is a
vasodilator), endothelin (vasoconstrictor), and nitric oxide (vasodilator)
• PERFORM GLUCONEOGENESIS (only the liver performs more than the kidneys)
o Gluconeogenesis is the production of glucose from non-carbohydrates such as, amino acids
• EXCRETE DRUGS AND TOXINS from the body fluids
What is the anatomic location and size of the Kidneys, and what organ sits on top of them?
• The kidney location is in the retroperitoneal (behind the peritoneal cavity), underneath ribcage (protected by
the ribcage)
• The kidneys should be about the same size; the average adult kidney size is 11 – 13 cm (longitudinally)
• There should be NO MORE THAN A 1.5 cm difference or greater difference between the kidneys
• If there is a ≥1.5 cm difference between the two kidneys; one is to large or one is to small (you need to investigate why)
• Adrenal gland sits on top of the kidneys; they have their own blood flow (BF), autonomic innervation, and lymphatic circulation
o The adrenal glands are actually completely separate organs from the kidneys
* If the patient has a nephrectomy, its very important that the surgeon dissects and removes just the kidney
and not the adrenal gland that is sitting on top of the kidneys*
Describe the blood flow to and from the kidneys and the indications related to them.
• Blood flow:
o You can see the abdominal aorta; and the abdominal aorta is where the renal arteries divide and branch off to provide BF to the kidneys
o So as soon as the LV ejects blood, there is not to far of a distance before the kidneys are perfused
o The kidneys receive 20 – 25% of CO/ minute
o Based on size, the kidneys (that are about the size of your fist) receive a lot of BF and are very vascular
structures
o You also see the renal veins coming off the kidneys and emptying into the inferior vena cava (IVC)
§ It is just as important to have unobstructed out-flow of blood as it is to have unobstructed in-flow of
blood (from the renal arteries)
§ If you have a tumor that obstructs the inferior vena cava and the renal veins, that increases the
pressure within the kidney; when the pressure within the kidney increases, that decreases that amount of BF to that kidney
o Another mechanism that helps propel urine from the kidneys to the bladder is?
gravity
Describe the urinary bladder.
• Urinary bladder
o Smooth muscle pouch
o As urine fills up the urinary bladder, it causes a reflex dilation; so the pressure does not rise in the urinary bladder in direct relation with the volume
o At some point the volume is going to cause such a pressure that it sends afferent impulses to your brain
that says you need to urinate
o Then you have the parasympathetic nervous system which contracts the bladder and relaxes the internal
sphincter
o The external sphincter is (hopefully/ usually) in voluntary control
• The R kidney does sit a little ___ than the L kidney (because of the liver)
lower
CARDIOVASCULAR – KIDNEY INTERRELATIONSHIPS • Renal fraction: \_\_\_\_\_ of CO perfuses kidneys each minute • With average CO: Renal blood flow – \_\_\_\_\_ ml/min. • Altered RBF = altered renal function
- 20 - 25%
* 1000 - 1200 ml/min
The kidneys are enclosed in this thick fibrous
tissue called the _____ _____.
RENAL CAPSULE
What is the function of the renal capsule?
o Helps enclose and protects the kidney
o If the kidney bleeds (like from a percutaneous renal biopsy), that renal capsule will hold that blood in; that can
be very detrimental to the kidney because that blood increases and puts pressure on the tissue (of that kidney) that will ultimately lead to ischemia
Kidneys are divided into the ___ and
___.
cortex and medulla
Renal artery branches off of the ___ ___.
abdominal aorta
The renal artery branches into what other arteries?
segmental arteries (superior, middle, and inferior)
o Superior provides BF to the superior
aspect of the kidney; middle to middle;
inferior to inferior
The renal vein delivers ___ blood back to the IVC.
deoxygenated
If you look at the renal pyramid here (urine is formed) you see these little dots in the membrane called the ___ ___.
• Urine empties thru the papilla into a ___ ___; and the minor calyces empty into their own ___ ___.
- Renal Papill
- Minor Calyx
- Major Calyx
o That urine is then transported in thru the ureter down to the urinary bladder
Trace blood flow from the left ventricle through the kidneys and then back to the mitral valve.
FROM THE LV BACK TO THE RA ** YOU WILL SEE THIS AGAIN **
LEFT VENTRICLE ->AORTIC VALVE -> ASCENDING AORTA -> ARCH OF THE AORTA ->DESCENDING THORACIC AORTA (PIERCES THE DIAPHRAGM) ->ABDOMINAL AORTA->BRANCHES INTO THE L & R RENAL ARTERIES ->SEGMENTAL ARTERIES (SUP, MID, INF) ->INTERLOBAR ARTERIES -> ARCUATE ARTERIES -> INTERLOBULAR ARTERIES -> AFFERENT ARTERIOLES -> GLOMERULUS -> EFFERENT ARTERIOLES -> PERITUBULAR CAPILLARIES ->VASA RECTA -> INTERLOBULAR VEINS -> ARCUATE VEINS -> INTERLOBAR VEINS ->RENAL VEIN -> INFERIOR VENA CAVA -> RIGHT ATRIUM -> TRICUSPID VALVE ->RIGHT VENTRICLE -> PULMONIC VALVE -> PULMONARY ARTERIES -> PULMONARY CIRCULATION -> PULMONARY VEINS -> LEFT ATRIUM -> MITRAL VALVE
What is the blood flow specifically through the kidneys?
1ST RENAL A. 2ND SEGMENTAL A. 3RD INTERLOBAR A. 4TH ARCUATE A. 5TH INTERLOBULAR A. 6TH AFFERENT ARTERIOLES 7TH GLOMERULUS 8TH EFFERENT ARTERIOLES 9TH PERITUBULAR CAPILLARIES 10TH VASA RECTA 11TH INTERLOBULAR V. 12TH ARCUATE V. 13TH INTERLOBAR V. 14TH RENAL V.
What is the functional unit of the kidneys?
Nephron
• Starting at the BOWMANS CAPSULE (completely surrounds those glomerular capillaries)
• The Bowman’s capsule then becomes the ___ ___.
o First you have the ___ proximal tubule
o Convoluted proximal tubule then becomes the ___ proximal tubule
• It then thins out and becomes the ___ ___ ___ ___ ___
o AKA the ______?
• The loop of Henle makes a hairpin turn; this is the ___ ___ ___ ___ ___.
o AKA the _________?
- PROXIMAL TUBULE
- CONVOLUTED
- STRAIGHT
- THIN DESCENDING LOOP OF HENLE
- concentrated segment
- THIN ASCENDING LOOP OF HENLE
- passive diluting segment
• The lumen of the tube then gets larger; this is the _____ _____ _____ _____.
o AKA the ____________?
• Then the ___ ___
o not really discussed much because the ___ distal tubule is very similar in function and structure to
the thick ascending limb of the loop of Henle
o and the ___ distal tubule is very similar in function and structure to the ___ ___ ___.
- THICK ASCENDING LIMB OF THE LOOP OF HENLE
- active diluting segment
- DISTAL TUBULE
- EARLY
- LATE
- CORTICAL COLLECTING TUBULE
AFTER THE DISTAL TUBULE WE HAVE THE ___ ___ ___?
• What is the result once the tubular filtrate leaves the medullary collecting duct?
- MEDULLARY COLLECTING DUCT
* urine
• In the adult, the kidney has how many nephrons?
- 1 – 1.25 million nephrons (2 – 2.5 million if you have both kidneys)
The kidney is divided into a ___ and the ___
cortex and medulla
There are two types of nephrons, what are they?
There are two types of nephrons
o CORTICAL nephrons (on the R side)
o JUXTAMEDULLARY nephrons (on the L side)
What is the characteristics of Cortical nephrons?
§ They are called the cortical nephrons because the
majority of the components of that nephron are located within the cortex of the kidney
§ 85% of nephrons are cortical
What is the characteristics of Juxtamedullary nephrons?
§ These nephrons (as you notice) have long thin
loops of Henle that dive deep deep down into the
medulla
§ Account for the other 15% of our nephrons
§ Responsible for determining the final urine
volume and concentration
Vasa recta lie right next to those long thin ___ ___ ___.
- loops of Henle
The glomerulus contains how many capillaries?
The glomerulus is ~ 12 – 24 capillaries
The Bowman’s capsule is the beginning of the___ ___ ___; it completely surrounds the glomerular
capillaries
-lumen of the tubule
The distal tubule (on each nephron) lies right in between the ___ ___ ___.
o The distal tubule actually comes into contact with the ___ arteriole
- afferent and efferent arterioles
- afferent
There are two different types of specialized cells that are collectively referred to as the ___ ___.
JUXTAGLOMERULAR APPARATUS
• The first group of cells are in the distal tubule itself
and they are called the ___ ____.
• The cells that surround the afferent arteriole are called
juxtaglomerular cells; those are the cells that secrete ___.
- MACULA DENSA
- RENIN
• Now lets look at the different layers of tissues that the tubular filtrate has to traverse to get from the glomerular
capillaries into the lumen of the tubule
o Because that’s out goal…………………………..?
-we want to filter the plasma from the glomerular
capillaries into the lumen of the tubules so that the kidneys can perform their function
The lumen of the glomerular capillaries has blood in it and it has three layers which are?
• This is the lumen of the capillary; it has blood in it • There are three layers: O CAPILLARY ENDOTHELIUM* O BASEMENT MEMBRANE* O PODOCYTE CELL PROCESSES* * These are the three layers that you have to get through to move filtrate from the glomerulus, into the Bowman’s capsule, and into the tubular filtrate
What is the significance of the opening that are located in the Capillary Endothelium of the glomerular capillaries? They are called? They allow what through and prevent what substances from passing through?
• Lets start with the first layer; the CAPILLARY ENDOTHELIUM
o They have these openings of a certain size and they’re actually larger than the openings in normal capillaries (that’s why they’re not called pores)
§ They’re called FENESTRAE (larger than normal openings)
§ Under normal conditions, RBCs, WBCs, platelets should not get through fenestrae in the capillary endothelium
§ Albumin SHOULD be able to get thru
What is the significance of the opening that are located in the BASEMENT MEMBRANE of the glomerular capillaries? They are called? They allow what through and prevent what substances from passing through?
o The next layer is the BASEMENT MEMBRANE; it has openings of a certain size that allows certain substances to either filter or not to filter through
§ Also a selectively permeable membrane
§ Don’t allow (RBCs, WBCs, or platelets) to get thru
§ Albumin should get thru
§ However, the basement membrane is strongly lined with negative charges
§ Albumin is a negatively charged protein
In regards to the basement membrane, what prevents albumin from passing through?
§ Albumin is a negatively charged protein
Q. What do like charges do to each other? They repel each other.
§ It’s the neg charge on the basement membrane that prevents albumin from being filtered from the
glomerulus into the Bowman’s capsule and then into the tubule
§ Based on size, albumin should be able to filter; it’s the negative charges on the basement membrane
that repel the negatively charged albumin
o The final layer of the Glomerular capillaries is the ___ ___.
§ They have these little foot processes that are called ___ ___.
o The final layer is the PODOCYTE CELL PROCESSES
§ They have these little foot processes that are called FILTRATION SLITS
v Filtration slits are of a certain size that allows some substances to pass and some not to pass
§ This is yet another layer that has to be traversed to get form the glomerulus to the Bowman’s capsule
Trace the flow of solute from the Glomerular capillaries to the proximal tubules.
CAPILLARY ->CAPILLARY MEMBRANE (FENESTRAE) -> BASEMENT MEMBRANE ->PODOCYTE CELL PROCESSES (FILTRATION SLITS) -> BOWMAN’S CAPSULE -> PROXIMAL TUBULE
WHAT ARE THE DETERMINANTS OF NET GLOMERULAR FILTRATION PRESSURE AND GFR?
DETERMINANTS OF NET GLOMERULAR FILTRATION PRESSURE AND GFR:
-GLOMERULAR CAPILLARY HYDROSTATIC PRESSURE =
FAVORS FILTRATION
-BLOOD COLLOID OSMOTIC PRESSURE =OPPOSES FILTRATION
-BOWMAN’S CAPSULE HYDROSTATIC PRESSURE = OPPOSES FILTRATION
What is the characteristics of Glomerular Capillary Pressure?
• The first pressure is the GLOMERULAR
CAPILLARY PRESSURE (GCP) or
GLOMERULAR CAPILLARY HYDROSTATIC
PRESSURE (GCP)
o GCHP is based on the amount of BF into the
glomerulus; increase in BF/ blood volume is going to increase the pressure against the walls of the glomerulus and increase capillary hydrostatic pressure
o That FAVORS filtration from the glomerulus into Bowman’s capsule
What is the characteristics of Blood Colloid Osmotic Pressure?
• Then we have the BLOOD COLLOID OSMOTIC PRESSURE (BCOP); which is created by the proteins in the blood, such as albumin
o That OPPOSES filtration from the glomerulus into Bowman’s capsule
What is the characteristics of Bowman’s Capsule Hydrostatic Pressure?
• Finally we have BOWMAN’S CAPSULE HYDROSTATIC
PRESSURE or CAPSULE PRESSURE (CP)
o Fluid and solutes are being filtered from the glomerulus into Bowman’s capsule; so there is fluid in there and that causes pressure and that opposes filtration from the glomerulus into Bowman’s capsule
How is net glomerular filtration pressure determined?
• To determine net glomerular filtration pressure, we have to take the one pressure that favors filtration (GCP)
and subtract from it the two pressures that oppose filtration (BCOP + CP)
• So in this example the GCP is 50 mm Hg and BCOP is 30 mm Hg and the CP is 10 mm Hg
o Net GFP (in this example) is 10 mm Hg; (this is animal numbers and you do not need to remember these
numbers)
What is the average GFR in adults?
AVERAGE GFR IN ADULTS
• 100 – 125 ml/min. is filtered each min from ALL of the glomerular capillaries into the Bowman’s capsules
(not each one) or ~ 180,000 ml/24-hours (180 liters/24-hours)
• 98 – 99% of filtrate reabsorbed from tubules into peritubular capillaries and back to systemic circulation
• THUS, AVERAGE 24-HOUR URINE OUTPUT: 1 – 2 LITERS/24-HOURS
REGULATION OF RBF AND GFR
• GFR remains fairly constant despite changes in (BP); anywhere from MAP of ~ 50 – 70 mmHg to 180 mmHg
o This is termed ___ ____: maintaining a constant GFR to maintain kidney function
-auto regulation
What are two ways that auto regulation is performed to keep a constant GFR?
o Kidneys do that a couple of different ways; one is through the SYMPATHETIC NERVOUS and the TUBULOGLOMERULAR FEEDBACK
How does the sympathetic nervous system provide auto regulation of GFR?
• SYMPATHETIC NERVOUS SYSTEM
o Innervates both afferent and efferent arterioles
o Constriction (alpha-1 receptors): under extreme circumstances such as trauma and/ or an outpouring of
large amounts of catecholamines, that can result in a decreased glomerular blood flow and GFR
o So when you have a sick pt and they have an outpouring of catecholamines to try to maintain their BP,
that release of EPI and NE act on the alpha–1 receptors causing vasoconstriction and thus decreasing
glomerular BF, that decreases GCP which decreases GFR/ renal function
o That’s one of the reason why traumatized or burn pts end up in renal failure; because they have an
outpouring of catecholamines which constrict the afferent arteriole and decrease the BF into the kidneys
How does the Tubuloglomerular feedback (TGF) provide auto regulation of GFR?
- Through Macula densa cells of distal tubules
- Through Juxtaglomerular cells of afferent arterioles
How do the Macula dense cells of the distal tubes provide auto regulation of GFR?
o Macula densa cells of distal tubules
§ You have the distal tubule that lies directly against the afferent arteriole
§ Macula densa cells (in the distal tubule) monitor the Na content of the tubular filtrate and the monitor the tubular filtrate flow rate
§ If either of those decrease, the macula densa will then send a message to the Afferent arteriole which causes afferent arteriole dilation
v I’m not quite sure what neurotransmitter that is; a good case could be made for nitrous oxide
§ MACULA DENSA: MONITORS NA CONTENT and TUBULAR FILTRATE
§ SENDS MESSAGE TO AFFERENT ARTERIOLE TO DILATE
§ 1st MESSAGE
How do the Juxtaglomerular cells of the distal tubes provide auto regulation of GFR?
o Juxtaglomerular cells of afferent arterioles
§ Efferent arteriole constriction mediated by renin-angiotensin II mechanism
§ 2nd message sent is to the juxtaglomerular cells of afferent arterioles
§ They secrete renin; renin leads to the synthesis of angiotensin II
§ The EFFERENT arterioles have lots and lots of angiotensin II receptors on it
So what is the net result of the auto regulation of GFR of Tubuloglomerular feedback?
o SO, you have AFFERENT arteriolar DILATION and EFFERENT arteriolar CONSTRICTION, with the
glomerulus right in the middle
§ This INCREASES BF IN and DECREASES BF OUT; which INCREASES GCP and GFR
§ More fluid is going to be filtered from the glomerulus into Bowman’s capsule because of AFFERENT art. DILATION and EFFERENT art. CONSTRICTION
o Helps maintain glomerular pressure and GFR
What is the indirect method of renin secretions from the SNS?
o AGAIN: THE INDIRECT METHOD OF RENIN SECRETION FORM THE SNS
1) SNS releases NE & EPI which act on alpha–1 receptors on the smooth muscle of the afferent arterioles causing constriction
2) This decreases the blood entering the glomerulus
3) Which decreases the glomerular capillary hydrostatic pressure
4) Which decreases filtration into Bowman’s capsule
5) Which decreases the tubular filtration flow rate as well as the tubular filtrate Na content
v Remember the MACULA DENSA cells monitor this last step
6) Macula densa sends a message to the juxtaglomerular cell to secrete renin
What is the direct method of renin secretions from the SNS?
o The JG cells have beta–1 receptors that when they become activated, they secrete renin
o So when you give a beta–blocker, it not only decreases their HR and strength of contraction, it blocks
these beta–1 receptors on the JG cells
§ which decreases renin, decreases angiotensin II (which is a potent vasoconstrictor); yet another way
that you decrease a pt’s BP when you give a BB
• Anything that Decreases sodium and/or decreased tubular filtrate flow rate at macula densa of distal tubule
will stimulate renin secretion
————————————————————————————
o THIS IS THE DIRECT METHOD OF RENIN SECRETION
• Renin is secreted by the JG cells (of the juxtaglomerular apparatus) which converts ANGIOTENSINOGEN (a
protein that is synthesized in the liver) into ANGIOTENSIN I
• ANGIOTENSIN CONVERTING ENZYME (ACE) converts angiotensin I into ANGIOTENSIN II
o ACE comes from the lungs primarily; its not the lungs
specifically, but it is the small arterioles in the endothelial cells of the lungs
o Lungs have the largest conglomeration of small arterioles (because of the vast capillary network) which leads to the secretion of ACE
o ACE also decreases bradykinin; by decreasing bradykinin you’re decreasing a vasodilator which leads to
an increase in MAP (which is our final goal here)
What is the net effects of TGF?
• Afferent arteriole dilation = increased blood flow and increased pressure in glomerulus
• Efferent arteriole constriction = decreased outflow of blood from glomerulus and increased pressure and
glomerulus pressure
• Increased glomerular pressure = enhanced GFR
What are the 3 processes involved with the GLOMERULAR AND TUBULAR PROCESSES?
- Glomerular filtration
- Tubular reabsorption
- Tubular secretion
Describe Glomerular filtration:
• THREE factors involved in Glomerular filtration
1) Glomerular capillary hydrostatic pressure
(FAVORS FILTRATION)
2) Blood colloid osmotic pressure
(OPPOSES FILTRATION)
3) Bowman’s capsule hydrostatic pressure
(OPPOSES FILTRATION)
Describe Tubular reabsorption:
• Tubular reabsorption
o Lumen of tubule → peritubular capillaries
o Once the tubular filtrate gets into the lumen of
the tubule, it’s then transported along the tubule
and at some point solutes and/ or H2O may be reabsorbed
§ Reabsorption: the movement of H2O and/ or solutes from the lumen of the tubule, back into the peritubular capillaries and back into the systemic circulation
• Reabsorption can occur at any point from the proximal tubule all the way to the end of the medullary collecting duct
Describe Tubular secretion:
• Tubular secretion
o Peritubular capillaries → lumen of tubule
o Secretion: the movement of fluid and/ or solutes from the peritubular capillaries back into the lumen of
the tubule
o Don’t confuse SECRETION with EXCRETION; excretion is the elimination of urine from the body or from the kidneys
• Each solute has its own filtration, reabsorption, and secretion properties; everything is not reabsorbed and
secreted at the same amount
What defines the amount of kidney clearance?
CLEARANCE
• Amount of solute filtered from glomerulus into tubular lumen
• MINUS total amount reabsorbed from filtrate of tubular lumen into blood of peritubular capillaries
• PLUS total amount secreted from blood of peritubular
capillaries into filtrate of tubular lumen
• EQUALS amount excreted into the urine (CLEARED by the kidneys)
• Example:
o 100mg of solute X is filtered from the glomerulus into the lumen of the tubule
o 50mg of that is reabsorbed
o 25mg (additionally) is secreted from the peritubular
capillaries back into the lumen of the tubule
o How much of that substance is going to cleared or excreted by the kidneys? 75mg
How is creatine clearance used for a clinical estimate of GFR?
• We can do this because Creatinine (a byproduct of muscle metabolism) is readily filtered from the
glomerulus into tubular lumen
• 10% additional creatinine secreted from the peritubular capillaries into the lumen of the proximal tubule
• Zero reabsorption of creatinine from tubular lumen
• Thus, creatinine clearance can be used as reasonably accurate clinical assessment of GFR and we use GFR
for a measure of overall kidney function
Identify this creatine clearance formula:
• Formula:UrVol (ml/min.) x Ur Cr (mg/dl)
SCr (mg/dl)
CREATININE CLEARANCE: 24-HOUR URINE COLLECTION METHOD
• Note that mg/dl cancel, so results are ml/min.
• Thus, CrCl and estimated GFR ~ 130 ml/min.
(Each min. 130 ml of blood has all of its creatinine cleared by the kidneys into the urine)
Identify this creatine clearance formula: • Formula:(140 – age in years) x (body wt. in kg) 72 x (SCr in mg/dl) • 140 & 72 are constant • FOR FEMALES, MULTIPLY RESULTS BY 85% • Overestimates GFR and renal fx in obese and fluid overloaded pts
CREATININE CLEARANCE: COCKCROFT-GAULT METHOD
Movement from glomerulus into Bowman’s capsule?
FILTRATION:
Movement of H2O and/ or solutes from the lumen of the tubule, back into the peritubular capillaries and back into the systemic circulation
REABSORPTION:
Movement of fluid and/ or solutes from the peritubular capillaries back into the lumen of
the tubule
SECRETION:
In the proximal tubule, the tubular filtrate is just simply a ___ ___; so it has the same ___ and same ___ as the plasma.
- plasma filtrate
- composition
- osmolality
In the proximal tubule (PT––the very first segment past the Bowman’s capsule), the tubular filtrate is simply
a plasma filtrate, so same composition and osmolality as plasma. What is the osmolality?
o About ~ 300 mOsm/L
What are the byproducts of metabolism that are found in the proximal tubules(4)?
• Byproducts of metabolism: o Urea o Creatinine o Other metabolic wastes o Drug metabolites
It starts with the proximal convoluted tubule that
becomes the ___ ___ ___ segment
• Then it becomes the ___ ___ ___ which is the ___ segment.
- proximal straight tubule
- thin descending limb of loop of Henle
- (concentrating segment)
After the thin descending limb of the loop of Henle, it makes the hairpin turn and becomes the ___ ___ ___ which is the ___ segment.
• Then it becomes the ___ ___ ___ which is the ___ segment.
- thin ascending limb of loop of Henle
- (passive diluting segment)
- thick ascending limb of loop of Henle
- (active diluting segment)
After the thick ascending limp of loop of Henle, Next is the ___ ___ ___ – similar (in
function and structure to) to the ___ ___ ___
• Then that becomes the ___ ___ ___ and then the
___ ___ ___
• And last is the ___ ___ ___.
- early distal tubule
- thick ascending limb of loop of Henle
- late distal tubule
- cortical collecting tubule
- medullary collecting duct
Tubular filtrate becomes urine after leaving the
___ ___ ___.
medullary collecting duct
Proximal convoluted tubule histology?
o Thick, cuboidal, endothelial cells
o Top (of picture) is facing the lumen of the tubule
§ usually referred to as the luminal border
§ made up of villi and microvilli (also called brush border––because it looks like the bristles of a brush) which help increase the surface area of the cells
dramatically
v which is very important because one of the major functions of these cells is to rapidly reabsorb solutes
v more surface area, the greater the ability of those cells to perform its function
o Bottom is facing the interstitial space
§ referred to as the basal border
o Has a large nucleus; suggesting that lots of DNA are being synthesized
o Has lots of mitochondria for ATP for active transport of solutes across the cell membrane, from the lumen of the tubule, eventually into the interstitium, and eventually into a peritubular capillary for reabsorption
o You also can see some transport proteins which are also involved in the reabsorption of solutes, from the lumen of the tubule, etc………..
Descending loop of Henle histology?
o Another name for this section is the concentrating segment
§ called this because at this segment, H2O is moving out and solutes are staying in; so the contents in the lumen
of the tubule are becoming concentrated
o These cells are very thin, flat cells that aid
in concentrating the tubular contents
o Have hardly any brush border
o Small nucleus; not many mitochondria
o Because we are just concentrating at this
point
Distal convoluted tubule histology?
o This would be the early distal tubule
o This is very similar in form and structure
to the THICK ascending limb of the loop
of Henle; which I called the active diluting
segment
o Look at how many mitochondria that are lining the basal border of those cells; those are used for making
many, many ATP for LOTS of active transport
o Lots of active transport of Na, K, and Cl at this point of the tubule
o Hence the name of the ACTIVE DILUTING SEGMENT; because its actively transporting Na, K, and Cl
from the lumen of the tubule, out into the interstitium to be reabsorbed (eventually)
Medullary collecting duct histology?
o These cells can change their permeability to H2O dramatically
o They can be almost completely permeable to H2O or impermeable to H2O
Q. What determines the permeability to H2O?
A. Either the presence or absence of antidiuretic hormone (ADH)
v If ADH is present, these cells become VERY permeable to H2O, and H2O is reabsorbed from the medullary collecting duct, back into the interstitium, back into the
peritubular capillaries to be returned to systemic circulation
v If ADH is NOT present, these cells are IMPERMEABLE to H2O and will stay in the lumen of the medullary collecting duct and is excreted into the urine
What is the sequence of blood flow through the kidneys?
1ST RENAL A. 2ND SEGMENTAL A. 3RD INTERLOBAR A. 4TH ARCUATE A. 5TH INTERLOBULAR A. 6TH AFFERENT ARTERIOLES 7TH GLOMERULUS 8TH EFFERENT ARTERIOLES 9TH PERITUBULAR CAPILLARIES 10TH VASA RECTA 11TH INTERLOBULAR V. 12TH ARCUATE V. 13TH INTERLOBAR V. 14TH RENAL V.
If we constrict the afferent arterial, what would that do to the glomerular hydrostatic pressure?
The afferent arteriole leads into the glomerular capillaries, so if they are constricted that will decrease blood flow into the glomerular capillaries which will decrease hydrostatic pressure thereby decreasing GFR.
How do you calculate net Glomerular Filtration Pressure?
• To determine net glomerular filtration pressure, we have to take the one pressure that favors filtration (GCP)
and subtract from it the two pressures that oppose filtration (BCOP + CP)
• So in this example (picture ì) the GCP is 50 mm Hg and BCOP is 30 mm Hg and the CP is 10 mm Hg
o Net GFP (in this example) is 10 mm Hg; (this is animal numbers and you do not need to remember these
numbers)
GCP=glomerular capillary pressure
BCOP=Blood Colloid Osmotic Pressure
CP=Capsule Pressure(Bowman’s Capsule Hydrostatic Pressure)
Secondary active co-transport, how does it happen?
- 2 substances bind to a protein transporter & it transports those substances in the same direction.
What has to be present for secondary active co-transport to occur?
Na-K pump, which is found on basal border. It’s pumping 3 Na+ out & 2 K+ in, creating electrochemical (EC) gradient for Na
How is sodium reabsorbed in the proximal tubule?
Tubular lumen, PT cell, interstitial space & PTC. On the basal border we have Na-K pump, which pumps 3 Na+ out & 2 K+ in, creating EC gradient for Na+.
o Na+ moves from tubular lumen into the cell into the interstitium (pumped out by Na-K pump) & then
reabsorbed back into PTC.
o Important that Na-K pump is working à if not, then can’t have secondary active co-transport.
How is Na:Amino Acids transported via secondary active co-transport?
have transport protein on the tubular lumen. Transport protein has binding sites for 1 amino acid & Na+. Should be Na-K pump on the basal border (it’s missing), which is needed to create EC gradient for Na+.
o That transport protein transports Na+ with its EC gradient & amino acid against it concentration gradient. Eventually, amino acid moves to interstitium & reabsorbed back into PTC. Na+ will be pumped out of peritubular cell by Na-K pump & reabsorbed into PTC as well.
o Under normal conditions, 100% of amino acids are reabsorbed by PT through secondary active cotransport
of Na+ & amino acids
How is Na:Glucose transported via secondary active co-transport?
it’s the same process as before, but using glucose instead of amino acids.
o Transport protein on lumenal border as a binding site for glucose & Na+.
o On basal border there is a primary active Na-K pump (not pictured) to create EC for Na+
o Na+ moves with its EC gradient & glucose moving against its concentration gradient. Eventually, Na+ & glucose are both reabsorbed back into PTC.
o Under normal conditions, 100% of filtered glucose is reabsorbed by PT through secondary active cotransport
of Na+ with glucose.
How does secondary active counter transport differ from secondary active co-transport?
Secondary active counter-transport does the same thing as active co-transport, except the substances are
moving in opposite directions
What is an example of secondary active counter transport?
Example: secondary active counter-transport of Na+ & H+ ions in PT cell. That is the start of how kidneys
regulate acid-base balance (will talk about next
quarter)
• 3rd pic to R: we have a PT cell. Tubular lumen has
a transport protein. Primary active Na-K pump on
basal border à 3 Na+ out & 2 K+ in, creating EC
gradient for Na+. Na+ moves with its EC gradient
& H+ ions are pumped against its concentration
gradient into tubular lumen to be excreted in urine. That’s the beginning of acid-base balance by the kidneys.
If the patient has increased circulating levels of ADH secondary to volume depletion and those medullary collecting duct cells are max permeable to water, what segment of tubule is most water reabsorbed?
Proximal tubule(65-70%)
How do you calculate tubular load of glucose?
• BG x GFR = TLOG
• Example:
o BG = 125 mg/dl
o GFR = 100 ml/min
§ Units of measurement need to be same. Convert mL to dL by dividing by 100.
o TLOG = 125 x 1 = 125 mg/min.
o If this pt has normal reabsorption capacity, should they lose any glucose into urine? No, bc TTM is usually 320 mg/min.
• Example:
o BG = 200 mg/dl
o GFR = 50 ml/min à convert mL to dL by dividing by 100.
o TLOG = 200 x 0.5 = 100 mg/min.
o This pt TLOG is actually less than the first pt & this pts glucose is more than the first pts. So, urine glucose is absolutely NOT an accurate estimate of BG bc it depends on GFR too.
How do you calculate the transport maximum of glucose lost in urine?
• Tubular transport maximum (TTM): when all the
glucose transporters in PT have become completely saturated & cant reabsorb any more glucose. TTM is
most people is 320 mg/min. So, once reach TTM you have a direct relationship b/t amt of glucose that
enters vs loss of glucose into urine. From this point on, past 320 mg/min you’re going to have a
corresponding increase in glucose lost into urine.
O EX: PT HAS TTM OF 320 MG/MIN. TLOG IS 500 MG/MIN. HOW MUCH GLUCOSE WILL BE LOST INTO URINE?
§ 500 MG – 320 MG = 180 MG/MIN OF GLUCOSE LOST INTO URINE.
If your IV infusion solution adds free water to the vascular compartment, would that increase or decrease ADH secretion?
decrease
When you sweat is it hyper or hypo osmotic?
- Hypo-osmotic
- Losing more water instead of solutes which increases ADH secretion.
There are ADH receptors in the hypothalamic thirst center that when ADH is secreted, what happens?
acts on these thirst centers which makes us want to drink water to bring body osm back down to normal
Which segment of tubule is filtrate the same as plasma osmolality?
Proximal tubule(water is reabsorbed, solutes are reabsorbed)
In which areas are tubular fluids always hyposmotic because of active transporters?
Ascending limb of Loop of Henle(pumping out na, K, 2 cl creating a hyposm tubular filtrate)
How does ADH works, whether it favors water reabsorptioin, what it does to body osm, urine ism, vasc volume and urine volume
?
Lets say there is 150 msg of substance X that is filtered into Bowman’s capsule, 75mg is reabsorbed, 40mg is secreted, what amount is excreted into urine?
-115mg
-CLEARANCE
• Amount of solute filtered from glomerulus into tubular lumen
• MINUS total amount reabsorbed from filtrate of tubular lumen into blood of peritubular capillaries
• PLUS total amount secreted from blood of peritubular
capillaries into filtrate of tubular lumen
• EQUALS amount excreted into the urine (CLEARED by the kidneys)
Does aldosterone favor increased or decreased vascular volume?
Aldosterone favors sodium reabsorbs, water moves with it, so aldosterone favors increase in vascular volume.
What would be the differential diagnosis of these symptoms and why? Hypertension, refractory to normal antihypertensives, mild hypernatremia, hypokalemia
Hyperaldosteronism; leads to vascular reabsorption(high sodium so hangs on to water), increased vascular volume, BP up
Tx would be aldosterone receptor blocker, spirolactone, triamterene.
How much free water is in NS?
0
How much free water is in 1/2 NS?
500 mls
How much free water is in LR?
0
How much free water is in plasmalyte?
0
How much free water is in 0.25% NS?
750mls
How much free water in D5W?
All of it
