1 - Renal 01 Flashcards
Water is added to the body in two main ways:
Ingestion (2 L)
Oxidation of Carbohydrates (200 ml)
What is insensible water loss?
How much is lost in a day?
Loss from the respiratory tract and skin
700ml/day
What is transcellular fluid?
specialized extraecllular fluid
pericardial fluid, synovial fluid, intraocular fluid etc
The more fat in the body, the _____ the % total body water weight
less
Obese persons and women have lower percent water
Conversely, infants and preemies have almost 75% water weight
The two largest compartments of the ECF are:
interstitial and plasma
The average blood volume of adults is ____ % body weight
7%
about 5L
The gibbs-donan effect causes a higher concentration of _____ in the plasma
positive cations
plasma proteins have a net negative charge and can’t diffuse across the capillary membrane, maintaining a constant negative charge within the capillary
In calculating osmotic gradients, what is an osmotic coefficient?
Most of the ions in the body have interionic forces which alter their movements across a gradient
the osmotic coefficient is factored in to account for these forces
What is the total osmolarity of the ECF and the ICF both?
of the plasma?
About 300 mOsm/L
Consistently 1-2 mOsm/L higher due to plasma proteins, which creates the oncotic pressure
The tonicity of a solution depends on:
the concentration of impermeant solutes
What is tonicity?
whether or not the solution will cause a change in the cell volume
How long does it take to achieve complete isotonic equilibrium in the body after drinking water
30 minutes
______natremia causes cellular edema
Hyponatremia
Becuase the skull is rigid, the brain can’t increase its volume more than ______ before herniating
10%
Osmosis demyelination can be avoided by:
limiting the correction of chronic hyponatremia to less than 10 to 12 mmol/L in 24 hours and to less than 18 mmol/L in 48 hours
______ natremia causes cell shrinkage
hypernatremia
What three conditions are especially prone to cause intracellular swelling?
- hyponatremia
- Depressed metabolic function
- Lack of adequate nutrition to the cell
If oxygen delivery to a cell is cut off, why does it swell?
cell membrane ionic pumps can’t function, which leads to increased intracellular sodium, which causes osmosis into the cell
The two main causes of extracellular edema are:
- abnormal capillary permeability
- lymphatic failure
What is the most common cause of interstitial fluid accumulation?
Increased capillary filtration
What causes increased capillary filtration
- increased capillary coefficient pressure
- increased capillary hydrostatic pressure
- Decreased plasma oncotic pressure
why does liver cirrhosis cause edema?
Decreased plasma protein concentration
In addition to decreased plasma proteins, why does liver cirrhosis cause edema?
compresses the portal vein, increasin hydrostatic pressure and causing acites
nonpitting edema is caused by ______ swelling
pitting edema is caused by ______ swelling
intracellular
extracellular/freeflowing fluid
Urea is a byproduct of _______
Amino Acid metabolism
How are kidneys involved in red blood cell production?
Secrete erythropoeitin, which stimulates RBC production in bone marrow stem cells
Most important stimulus for erythropoeitin release is hypoxia
Are the kidneys found within the peritoneal cavity
no, they lie behind it
Blood flow to the kidney accounts for what percentage of cardiac output?
22%
Describe the capillary beds of the renal circulation
Has two separate beds: the glomerular bed and the peritubular bed
Blood flows:
In through the afferent
Into the glomerular bed
Out of the glomerulus through the efferent
Into the peritubular bed
Trace a blood cell entering the kidney:
Renal artery
Interlobar arteries
Arcuate Arteries
Interlobular Arteries
Afferent Arterioles
Glomerulus
Efferent Arteriole
Peritubular capillaries
Can the kidney regenerate nephrons?
No
at age 80 years, many people have 40% fewer functioning nephrons than they did at age 40 years
How does the hydrostatic pressure in the glomerular capillary bed compare to other capillary beds?
Unusually high @ 60mmHg
What is Bowman’s Capsule?
The glomerular capillaries are covered by epithelial cells, and the entire glomerulus is encased by Bowman’s Capsule
Which part of the nephron contains bowman’s capsule, the distal tubule, and the macula densae?
The cortex
The smooth muscle of the bladder is called:
the detrusor muscle
From which spinal roots is the bladder innervated?
S2-S3
the pelvic nerves via the sacral plexus
What prevents urine from refluxing back into the ureter?
The ureter passes through the detrusor muscle, which occludes the ureter when it isn’t actively peristalsing
peristaltic contraction of the ureters is increased by _____ and decreased by ______
parasympathetic
sympathetic
What happens when a ureter becomes blocked?
Uretorenal reflex:
intense reflex constriction of the ureter
pain signals to kidney causes sympathetic reflex constriction of the renal arterioles
Urine Output decreases
What is an atonic bladder?
Lack of sensory nerve fibers from the bladder to the spinal cord
resulst in overflow incontinence
What is an automatic bladder?
When the spinal reflexes are intact, but the spinal cord above the sacral level is damaged
the spinal reflex works, but the brain can’t communicate with the bladder
What is a neurogenic bladder?
partial damage to the spinal cord that interrupts most of the inhibitory signals traveling to the bladder
frequent and relatively uncontrolled micturition
How is the rate of urinary excretion determined?
Urine = Filtration rate - reabsorption rate + secretion rate
Why is it abnormal to find glucose in urine?
Some nutritional substances like amino acids and glucose are completely reabsorbed from the tubules and do not appear in the urine, even though large amounts are filtered by the glomerular capillaries.
How much fluid is filtered every day?
How much is excreted?
About 180 L/day
About 1L/day
Means almost all fluid filtered is reabsorbed
How much protein is found in glomerular filtrate?
None (normally)
What percentage of the plasma flowing through the glomerular capillary bed is filtered with each pass?
About 20%
The glomerular membrane is _____ and ______ than other membranes
thicker and yet also more porous
Allows for high filtration and high specificity
Which is more easily filtered: negatively charged large molecules or positively charged large molecules?
Positively charged
the endothelium is lined with negatively charged proteins
What isn’t albumin filtered?
It’s actually small enough, but the positive charge on the proteoglycans of the basement membrane and podocytes repel it
How does increased resistance in the afferent arteriole effect GFR?
Increased resistance in the efferent ateriole?
Decreased GFR (less fluid entering the glomerulus)
Slight increase in efferent: Increased GFR (increases hydrostatic pressure in the glomerulus)
Severe increase in efferent: Reduced GFR
Why do the kidneys consume so much oxygen?
Active reabsorption of sodium
Most renal vascular resistence is a consequence of which three vascular areas?
Afferent arterioles
efferent arterioles
interlobular arteries
The kidneys can autoregulate to maintain normal GFR between what SBPs?
80 - 170 mmHg
Which part of the kidney receives the most blood flow: the cortex or the medulla
the cortex
Flow to the renal medulla is supplied by:
the vasa recta of juxtamedullary glomeruli
What is the primary role of the vasa recta?
Allowing for the production of highly concentrated urine
Mild to moderate sympathetic stimulation of the kidneys results in:
no change in GFR, but significant change in hormonal regulation
Strong activation of renal sympathetic nerves results in:
markedly decreased renal GFR
Increased prostaglandins will _____ GFR
Increase
Increases in circulating NE and Epi will _____ GFR
decrease
Which autacoid substance is present in pre-Eclampsia
Endothelin
Causes renal arteriolar constriction and decreased GFR
Angiotensin II primarily affects ______ arterioles.
Why?
Efferent
All areas of renal vasculature have receptors for Angiotensin II, but the afferent and glomerular capillaries have strong inhibitory substances present (nitric oxide and prostaglandins) which usually overrides the effect of angiotensin II
When does Angiotensin II production generally occur?
Why?
decreased arterial blood pressure and decreased volume
Efferent arteriolar constriction during these states results in increased hydrostatic glomerular pressure, which helps accomodate for the decreased flow entering the kidney
It prevents the GFR from decreasing due to decreased renal artery flow
Why is Angiotensin II’s effect on the efferent arterioles problematic?
The increased pressure reduces flow through the peritubular capillary bed, which increases the reabsorption of sodium and water
That’s great if the problem is cuased by volume depletion, but if it’s caused by heart failure it may make things worse
What is the juxtaglomerular complex?
Macula densa cells in the distal tubule and juxtaglomerular cells in the afferent and efferent arterioles lie next to each other, allowing communication and autoregulation
If there is decreased sodium concentration in the macula densa cells of the distal tubule, what happens?
the macula densa cells interpret the decreased sodium as a sign that flow through the loop of henle has decreased, allowing the reabsorption of more sodium
the macula densa cells communicate with juxtaglomerular cells in the afferent arteriole and cause vasodilation
the macula densa cells communicate with juxtaglomerular cells in both the efferent and afferent arterioles to release renin
Renin produces Angiotensin II which causes efferent arteriole constriction
What is a complication of using Angiontensin Inhibitors for blood pressure control?
You take away the kidney’s defense mechanism from severe hypovolemia
If the patient becomes hypovolemic, you can get severe kidney damage
What is the myogenic mechanism?
The ability of a vessel to resist stretch during increased arterial pressure
How do increased protein and hyperglycemia affect GFR?
Increase GFR
How is renal blood flow monitored in the kidney?
It really isn’t. The amount of sodium in the distal tubule is 99% of what controls renal autoregulation
Is GFR lower or higher in infants?
Lower
How much glucose is excreted from the kidneys each day?
Usually none
180 g/day is filtered
180g/day is reabsorbed
Name two products that extremely poorly reabsorbed in the kidneys
Creatinine and Urea
Glucose reabsorption is an example of ______ transport
Secondary Active
driven by the ion gradient created by the sodium pump
What are the cellular and paracellular pathways?
Two ways of getting from the interstitium of the kidney back into the blood (reabsorption)
Can occur through transport through the cell membrane (cellular)
OR between cell junctions (paracellular)
Sodium reabsorption in the kidney is an example of ______ transport
primary active
When a substance is reabsorbed, which two membranes must it cross?
- The tubular epithelial membrane (into renal interstitial fluid)
- The peritubular capillary membrane (back into the blood supply)
Describe the three steps of sodium reabsorption:
- Sodium moves down its electrochemical gradient through the luminal (apical) membrane
- Sodium is actively transported against its gradient across the basolateral membrane by Na-K ATPase
- Sodium is reabsorbed by the capillaries via ultrafiltration (which uses high hydrostatic pressure to drive ions and water across the membrane)
When is a substance said to undergo active transport during reabsorption?
If active transport or secondary active transport is used at any point, even though other points may involve passive transport
Sodium is said to be actively reabsorbed, even though it initially
How are proteins reabsorbed from the proximal tubule?
Pinocytosis
What is the transport maximum?
The maximum rate at which the solute can be transported across the membrane
What is the difference between threshold and transport maximum?
Why is there a difference?
The threshold is the point at which the substance will be excreted in urine. For glucose, some will be excreted whenever the blood glucose is greater than 200
BUT
the transport maximum is 375mg/min
WHY?
This happens because nephrons hit their transport max at different times. One nephron may be maxed out and its neighbor may not. Results in a little bit of glucose being excreted
Why don’t some substances that are actively reabsorbed exhibit a transport maximum?
What is this kind of transport known as?
Because they’re rate of reabsorption is driven by other factors (such as an actively created chemical gradient) and not a specific pump
Gradient-Time transport
Water moving across the tight junctions by osmosis also carries with it some of the solutes, a process referred to as:
solvent drag
At what point in the nephron do cell junctions tighten to the point that osmosis is dramatically reduced?
the ascending loop of Henle
Past the loop of henle, water reabsorption is controlled by:
aquaporins
the amount and status of aquaporins direclty controlls the amount of water reabsorbed
How does sodium reabsorption drive chloride reabsorption?
When sodium is actively transported, it creates a more negative charge in the interstitium, which creates a chemical gradient that Cl moves down
More than 90% of the waste nitrogen that is created by protein metabolism is excreted as:
urea
What percent of filtered water and sodium are reabsorbed in the proximal tubule?
65%
Why is the proximal tubule so good at reabsorbing?
- Epithelial cells in the PT have tons of mitochondria, enabling lots of active transport
- Extensive brush network and intercellular/base channels
Which segment of the loop of Henle has a thick epithelial cells and high metabolic activity?
the thick ascending segment
In the thick ascending loop, movement of sodium across the luminal membrane is mediated primarily by:
NKCC2
1-sodium, 2-chloride, 1-potassium cotransporter
co-transport protein in the luminal membrane
uses the potential energy released by downhill diffusion of sodium into the cell to drive the reabsorption of potassium into the cell against a concentration gradient.
loop diueretics act on which area of the loop of henle?
Thick ascending
Lasix and Bumex inhibit which carrier protein?
NKCC2
The thick segment of the ascending limb of the loop of Henle empties into the
distal tubule
The first portion of the distal tubule forms the _____
macula densa
Thiazide diuretics act on which protein transporter?
inhibit sodium-chloride cotransport
Principle cells reabsorb ____ and secrete ______
sodium
potassium
Potassium sparing diuretics act on ______ cells
Principle Cells
____ and _____ decrease urinary excretion of potassium and act as potassium sparing diuretics
Sodium channel blockers
Aldosterone Antagonists
__________play a major role in acid–base regulation and constitute 30% to 40% of the cells in the collecting tubules and collecting ducts
intercalated cells
Type A intercalated cells are especially important in:
eliminating hydrogen ions while reabsorbing bicarbonate in acidosis
A is for acidosis
Type B intercalated cells are especially important in:
secreting bicarbonate into the tubular lumen while reabsorbing hydrogen ions in alkalosis
B is for Basic
The permeability of the late distal tubule and cortical collecting duct to water is controlled by the concentration of:
ADH
In each nephron, what is the final site of urine processing?
The medullary collecting ducts
What is inulin?
polysaccharide used to measure GFR and water reabsorption
cannot be reabsorbed or secreted by the tubules
What is glomerulotubular balance?
Reabsorption increases when tubular load increases, which results in an unchanged reabsorption percentage
What is the difference between glomerulotubular and tubuloglomerular balance?
glomerulotubular: the tubules increase their reabsorption when they encounter increased inflow
tubuloglomerular: changes in the concentration of sodium in the macula densa cells constricts or dilates the afferent arteriole leading to the glomerulus
Increases in arterial pressure tend to _____ peritubular capillary hydrostatic pressure and _____ the reabsorption rate
raise
decrease
constriction of the efferent arterioles ______ glomerular capillary hydrostatic pressure and _____ peritubular capillary hydrostatic pressure.
increases
Decreases
An increase in resistance of the afferent or efferent arterioles ______ peritubular capillary hydrostatic pressure and tends to ______ reabsorption rate
decreases
increase
Why does an increases in peritubular capillary hydrostatic pressure reduce reabsorption?
Fluid less likely to flow into the capillary
fluid backs up inot the interstitium
increased pressure in the interstitium decreases osmosis and diffusion
reabsorption decreases
when pertitubular capillary reabsorption is increased, what is the effect on tubular reabsorption?
Why?
It is also increased
As water moves down its concentration gradient into the capillary from the interstitium, the concentration gradient in the interstitium increases.
As the concentration gradient in the interstitium increases, fluid moves down its concentration gradient from the tubule to the interstitium
forces that increase peritubular capillary reabsorption also increase:
reabsorption from the renal tubules
hemodynamic changes that inhibit peritubular capillary reabsorption also:
inhibit tubular reabsorption of water and solutes.
In kidney disease, GFR is very dependent on arterial pressure. Why?
Autoregulation is impaired
Raising the blood pressure will have almost a direct effect on urine output
ALDOSTERONE
Site of Action
Effect(s)
Principle cells of collecting tubule and duct
↑NaCl, H2O reabsorption
↑K+ secretion
↑H+ secretion
ANGIOTENSIN II
Site of Action
Effect(s)
Proximal tubule, thick ascending loop of Henle, distal tubule, collecting tubule
↑NaCl, H2O reabsorption
↑H+ secretion
ADH
Site of Action
Effect(s)
Distal tubule/collecting tubule and duct
↑H2O reabsorption
ANP
Site of Action
Effect(s)
Distal tubule/collecting tubule and duct
↓NaCl reabsorption
PARATHYROID
Site of Action
Effect(s)
Proximal tubule, thick ascending loop of Henle, distal tubule
↓PO4− reabsorption
↑Ca2+ reabsorption
What are the most important stimuli for aldosterone secretion?
Increased serum potassium
Increased Angiotensin II
What happens when there’s too little aldosterone?
Too much?
High potassium, low sodium (Addison Disease)
Low potassium, high sodium (Conn Syndrome)
Angiotensin II does three things:
- stimulates aldosterone
- constricts efferent arteriole
- directly stimulates sodium reabsorption in the proximal tubules, the loops of Henle, the distal tubules, and the collecting tubules
Why is it important that angiotensin constricts the efferent arteriole?
It allows the hydrostatic pressure in the glomerulus to increase, so the amount of filtration is increased
this helps offset the increased water and sodium retention
The body is able to get rid of bad shit even though lots of water and sodium is being retained
SNS activation ______ sodium reabsorption
increases
What hormone primarily determines urine concentration?
ADH
Tubular Fluid osmolarity is _____ in the proximal tubules
isosmotic
Tubular Fluid osmolarity is _____ in the ascending loop of henle
diluted
impermeable to water, even in the presence of ADH
regardless of whether ADH is present or absent, fluid leaving the early distal tubular segment is:
hypo-osmotic
What is the difference between specific gravity and osmolarity?
specific gravity is the total weight of particles in a solute
osmolarity is the total number of particles
What is required to form concentrated urine?
- Lots of ADH
- A high osmolarity in the renal medulla interstitial fluid
How does the renal medulla maintain an extremely high osmolarity?
countercurrent multiplier:
active transport of sodium and co-transport of potassium, chloride, and other ions from the thick ascending loop of Henle into the interstitium
continued inflow of new sodium chloride from the proximal tubule into the loop of Henle
