Week 4 Renal Flashcards
Where are the kidneys located?
Kidneys are in the posterior region of the abdominal cavity, behind the peritoneum. They lie on either side of the vertebral column, with upper and lower poles extending from 12th Thoracic vertebra to 3rd lumbar vertebra.
Define cortex of kidney
Outer layer of kidney, contains all the glomeruli, most of proximal tubules and some of the segments of the distal convoluted tubule
Define Medulla
Inner part of the kidney consisting of regions called pyramids
Define pyramids of kidney
Extend into the renal pelves and contain loops of Henle and collecting ducts
What are the renal columns
extension of the cortex, extend between the pyramids to the renal pelvis
What are the renal calyces
=chambers receiving urine from collecting ducts and form entry of renal pelvis (extension of upper ureter)
What is the structural unit of the kidney, and what is it composed of
Structure unit of the kidney is the lobe. Each love is composed of a pyramid and overlying cortex, with 14-18 lobes in each kidney
What is the functional unit of the kidney? Describe
Nephron is a tubular structure with: 1. Renal Corpuscle 2. Proximal convoluted tubule 3. Loop of Henle 4. Distal convoluted tubule 5. Collecting duct=all help with formation of urine
What are the 3 kinds of nephrons
(1) superficial cortical nephrons (85% of all nephrons), which extend partially into the medulla; (2) midcortical nephrons with short or long loops; and (3) juxtamedullary nephrons (about 12% of nephrons), which lie close to and extend deep into the medulla and are important for the concentration of urine
What is the glomerulus
The glomerulus is a tuft of capillaries that loop into the Bowman capsule (Bowman space), like fingers pushed into bread dough.
What do mesangial cells do
Mesangial cells (shaped like smooth muscle cells) secrete the mesangial matrix (a type of connective tissue) and lie between and support the capillaries. Mesangial cells also have phagocytic abilities=release inflammatory cytokines + can contract to regulate glomerular capillary blood flow
What does the renal corpuscle consist of (3 components)
Combo of glomerulus, the Bowman capsule, and mesangial cells (GBM)
Describe the 3 layers of the glomerular filtration membrane
The glomerular filtration membrane filters blood components through its 3 layers:
(1) an inner capillary endothelium (cells in continuous contact with the basement membrane + has pores)
(2) a middle basement membrane (glycoproteins + mucopolysaccharides)
(3) an outer layer of capillary epithelium (Podocytes from which pedicles (foot projections) stick to basement membrane)
Filtration slits=pedicles interlock with podocytes
Endothelium, basement membrane + podocytes covered with protein molecules with anionic (negative) charges=help with filtration of anionic proteins and prevention of proteinuria
The membrane separates blood of glomerular capillaries + fluid of Bowman space. Filters everything EXCEPT blood, plasma proteins
What blood source is the glomerulus supplied be? Where does blood drain?
Glomerulus: is supplied by the afferent arteriole and drained by the efferent arteriole.
What hormone do juxtaglomerular cells release
renin
Where are juxtaglomerular cells located
around the afferent arteriole where it enters the glomerulus
What is the macula densa? Where is it located?
Macula Densa: (sodium-sensing cells) located Between the afferent+ efferent arterioles on the distal convoluted tubule
What does the juxtaglomerular apparatus consist of? What is are its 3 functions?
Juxtaglomerular Apparatus=Juxta cells + Macula Densa
Function: 1. Control renal blood flow (RBF) 2. glomerular filtration 3. Renin secretion occurs here
Describe the proximal convoluted tubule
Proximal convoluted tubule: Consists of 1 layer of cuboidal epithelial cells+surface layer or microvilli=increases reabsorptive surface area **only surface with microvilli in nephron
Joins the Loop of Henle which extends into Medulla
Describe the loop of Henle
Loop of Henle: Cells of thick segment are cuboidal=transport solutes, no H2O—thin segment is thin squamous cells, no transport
Describe the distal convoluted tubule
The distal convoluted tubule: has straight and convoluted segments. It extends from the macula densa to the collecting duct
Principal cells: reabsorb sodium, secrete potassium
intercalated cells: secrete hydrogen, reabsorb potassium + bicarbonate.
Adjusts acid-base balance by excreting acid into the urine and forming new bicarb ions
Describe the collecting ducts
Collecting duct: a large tubule that descends down the cortex, through the renal pyramids of the inner and outer medullae, draining urine into the minor calyx
What is GFR
Glomerular filtration rate (GFR) – is the measurement of plasma filtration per unit of time.
How is GFR regulated?
GFR is autoregulated via the perfusion pressures (capillary hydrostatic pressure, oncotic pressure, hydrostatic pressure of Bowmans space) of the glomerular capillaries.
What substance cannot pass through the glomerular capilleries into Bowmans capsule?
The glomerular capillaries do not allow RBCs and plasma proteins to pass into the Bowmans capsule, because the glomerular filtration barrier consists of 3 layers that eliminate loss of RBC and prevent proteinuria. This then only leaves a small amount of filtrate (a combination of substances: water, solutes like Na+) to circulate in the tubules, approx. 125ml.
What hormones affect blood flow to the kidney?
Adrenaline and Angiotensin II increase arterioles (afferent and efferent) resistance which in turn decrease renal blood flow and decreases GFR. These hormones are stimulated in order to raise BP and stimulate reabsorption.
Atriopeptin (ANP) (secreted via Atria) and Brain Natriuretic Peptide (BNP) (secreted via ventricles) decreases arterioles resistance which in turn increase renal blow flow and increases GFR. These peptides are stimulated in order to help lower BP and excrete substances.
What is Autoregulation of Renal Blood Flow
-local mechanism with kidney – will keep renal blood flow and GFR constant over a range of systemic blood pressures (80mmHg – 200mmHg)
What is the myogenic mechanism?
Myogenic mechanism – smooth muscle cells contract when stretched because of high volumes/pressures of blood. Once cells are stretched, the afferent and efferent arterioles contract.
What is the Tubuloglomerular Mechanism
Tubuloglomerular Mechanism – involves distal convoluted tubule and glomerulus. The macula densa cells – chemoreceptors - sense when GFR is up or down based on quantity of Na+ or Cl- ions floating thru tubules.
-If increase in BP = Increase renal blood flow = increase GFR therefore more fluid and more dissolved ions reach macula densa which in response will release adenosine causing the afferent arteriole to constrict, decreasing GFR.
What is the vasa recta
Vasa Recta – network of capillaries that is the only blood supply to the medulla (contributes to formation of concentrated urine). The capillaries form loops and closely follows the loop of Henle.
Describe the process of urine formation
Glomerular Filtration: Movement of fluid and solutes across the glomerular capillary membrane into the bowman space
- Water, electrolytes (sodium, chloride, and potassium), and organic molecules (creatinine, urea, glucose) are filtered at the glomerulus.
- Protein free
Tubular reabsorption: Movement of fluids and solutes from the tubular lumen to the peritubular capillary plasma
reabsorption of h20 by osmosis- occurs when ADH is present
Reabsorption of sodium by active transport. More sodium is conserved when aldosterone is secreted
Glucose by active transport
Tubular Secretion: Transfer of substances from the plasma of the peritubular capillary to the tubular lumen
- Secretion of ammonia, hydrogen, and potassium by active transport.
What factors determine GFR
Factors determining GFR are related to the pressures that favour or oppose filtration.
Obstruction of outflow (ex. Strictures, stones, tumours) can cause an increase in hydrostatic pressure at bowman space and a decrease in GFR
Low levels of plasma protein in the blood can results in a decrease in capillary oncotic pressure resulting in an increase in GFR
Excessive loss of protein-free-fluid from vomiting diarrhea or use of diuretics can increase capillary oncotic pressure and decrease GFR
Where does urine concentration primarily occur
Urine concentration/dilution occurs primarily in the loop of Henle, distal convoluted tubules and collecting ducts
What determines final urine composition
Final urine composition is determined by the distal convoluted tubules and collecting duct according to what the body needs
What is the countercurrent exchange system
The production of concentrated urine involves a countercurrent exchange system in which fluid flows in opposite directions through the parallel tubes of the loop of Henle
What is substance is transported out of the ascending limb of Henle to the descending limb of vasa recta/ interstitium
NaCl
As urine flows _________________ in the collecting tubule, it encounters higher and higher concentrations of solutes in the interstitium. Hence it goes on losing water due to osmosis. This is how urine is concentrated.
downwards
Define tubular reasbsorption
Tubular reabsorption is the movement of fluids and solutes from the tubular lumen to the peritubular capillary plasma.
Define tubular secretion
Tubular secretion is the transfer of substances from the plasma of the peritubular capillary to the tubular lumen…for eventual excretion.
Define excretion
Excretion is the elimination of a substance in the final urine
Where is the primary site of sodium reabsorption
Proximal Convoluted tubule:
Primary site of sodium reabsorption.
What happens to drug elimination if renal tubules are damaged
Damage to the renal tubules results in retention and accumulation of metabolites and causes toxic effects.
What moves into the tubule in exchange for sodium ions?
Hydrogen ions move into the tubule in exchange for sodium ions
How is bicarb transported out of the tubule into the peritubular capillery?
Basically, hydrogen and sodium are positive ions that are required for the transport of bicarb from the tubule back into the peritubular capillary. In more detail: Hydrogen ions move into the tubule in exchange for sodium ions. These ions then combine with bicarbonate (HCO3) to form carbonic acid H2CO3 which can break down into Carbon dioxide and water to allow it to be absorbed from the tubular space into the tubular cell. Here it forms bicarbonate and hydrogen ions again but this time sodium ions join the bicarbonate ions as a sodium bicarbonate buffer (NaHCO3) to move it into the peritubular capillary. The reabsorption of the hydrogen ions as water means that there is not a large shift in pH in either the blood or the urine.
What mechanism is responsible for urine concentration? What does it rely on?
The Countercurrent exchange system is responsible for urine concentration and relies on a concentration gradient that causes the exchange of fluid.
T/F The concentration gradient in the kidney increased from the cortex to the medulla
T: The concentration gradient increases from the cortex to the tip of the medulla as you move down the descending limb of the loop of henle.
What part of the loop of henle is permeable to water?
descending
Where is water rebabsorbed from the tubular system? why?
As fluid in the tubular system descends in the medulla, the concentration gradient increases causing water to be reabsorbed from the tubular system. This occurs in the descending limb of the loop of henle because this area is only permeable to water (some passive transport of sodium and chloride is allowed, but not active transport).
What is transported in the ascending loop of Henle, and how
NaCl, active transport
Is the ascending loop of Henle permeable to water?
No
Describe the journey of tubular fluid throughout the whole loop of Henle. What does the end product look like?
As fluid in the tubular system descends in the medulla, the concentration gradient increases causing water to be reabsorbed from the tubular system. This occurs in the descending limb of the loop of henle because this area is only permeable to water (some passive transport of sodium and chloride is allowed, but not active transport). The result is that by the time the fluid reaches the bottom of the loop of henle where the concentration gradient is greatest, the fluid within the tubule is very concentrated because mostly sodium and chloride have remained in the tubule while water has been reabsorbed into the medullary interstitium.
As the fluid in the tubule rounds the corner and ascends the ascending limb of the loop of henle, the surrounding interstitium has a less and less concentration gradient. Active transport of sodium and chloride out of the tubule into the medullary interstitium occurs. However, water is not able to diffuse in this location. This results in relative dilution of the fluid in the tubule (but not an increase in volume!) In theory, the fluid within the tubular system has the same concentration at the top of the medulla, so where it enters from the proximal convoluted tubule and where it exits in the distal convoluted tubule. However, the volume has decreased because reabsorption of water and sodium chloride have occurred.
What happens to sodium and potassium in the DCT under the influence of aldosterone?
Sodium is readily reabsorbed here under the regulation of aldosterone.
Potassium is actively secreted here under the regulation of aldosterone and potassium concentration in body fluids.
What is the site of acid base balance? (what part of kidney)
DCt
How is acid eliminated in urine?
Hydrogen ions are secreted in the distal convoluted tubule to combine with ammonium and phosphate buffers to eliminate acid in the urin
What is the normal ph of urine
4.6 and 8
Why do we want acidic urine
protects against bacteria
What hormone is responsible for reabsorption of water before final excretion of urine? Where does this occur?
ADH in the collecting duct
Describe tubuloglomerual feedback (an autoregulation mechanism of the kidney)
Macula densa cells in the distal convoluted tubule sense changes in glomerular filtration rate (GFR) and the amount of filtered sodium. When the GFR and sodium concentration increase, this stimulates vasoconstriction in the afferent arteriole to decrease the GFR. The opposite is also true. This is called tubuloglomerular feedback which is an autoregulation mechanism in the kidneys. The result is the avoidance of large fluctuations of water and salt in the body.
What are the 3 major endocrine functions of the kidney
Vitamin D activation, EPO, renin
Describe the process of vit D activation by kidney
Vitamin D Activation (Hydroxylation)
Vitamin D is necessary for the absorption of calcium and phosphate by the small intestine
Activation is stimulated by Parathyroid Hormone
A decrease in plasma calcium level stimulates the secretion of parathyroid hormone
Parathyroid Hormone stimulates the following sequence of events to restore calcium levels:
Calcium mobilization from Bone
Synthesis of 1,25-dihydroxy-Vitamin D3
Absorption of calcium from the intestine
Increased Renal calcium reabsorption
Decreased Renal Phosphate reabsorption
Decreased Phosphate levels stimulate 1,25-dihydroxy-vitamin D3 formation and increased levels inhibit its formation
This results in compensatory changes in the phosphate absorption from bone and intestine
Describe the process of EPO production by the kidney
Stimulates Erythropoiesis in the blood marrow in response to hypoxia
Peritubular Fibroblasts, in the juxtamedullary cortex, sense decreased oxygen levels and produce EPO
How does renal disease impact EPO production
Chronic Kidney Disease can cause these cells to be non-functional and lack of EPO can cause anemia
What is urodilatin?
Is a natriuretic peptide
It is produced by cells in the distal convoluted tubule and collecting duct
It increases renal blood flow causing diuresis
Causes vasodilation, increased sodium and water excretion, and decreased blood pressure
It is an antagonist to the Renin-Angiotensin-Aldosterone System
Define hydrostatic pressure
Hydrostatic pressure = mechanical force of water pushing against cellular membranes
Force that PUSHES water
Describe colloid osmotic pressure
Colloid osmotic pressure = aka oncotic pressure; a form of osmotic pressure exerted by proteins, notably albumin, in a blood vessel’s plasma (blood/liquid) that usually tends to pull water into the circulatory system
Force that PULLS water
Describe tubuloglomerular feedback
Macula densa cells in the distal convoluted tubule are sensitive to flow rates and sodium concentration
If low flow rates or low sodium in DCT, macula densa cells signal for relaxation of the afferent arterioles (=more flow)
If high flow rates or high sodium in DCT, macula densa cells signal for construction of the afferent arterioles (=less flow)
Describe the myogenic mechanism
Myogenic mechanism in afferent arterioles
When BP increases, the smooth muscle around afferent arterioles are stretched and respond by contracting. This reduces incoming blood volume to protect the glomerulus from high BP damage
When BP is lower, the smooth muscle is relaxed to lower resistance and therefore increase flow to the glomerulus (maintaining normal GFR)
What do the macula densa cells do if low sodium is sensed in DCT?
relaxation of aff arterioles- more flow
BP is low. How does the myogenic mechanism help maintain normal GFR?
smooth muscle relaxes, therefore increased blood flow to glomerulus to maintain gfr
What happens to blood flow to kidneys when sympathetic nervous system (SNS) is stimulated?
Increases in sympathetic stimulation cause vasoconstriction of afferent arterioles and decreased blood flow through the kidneys
How does Angiotensin II decreased GFR rate? Why would it do this?
Angiotensin II decreases GFR rates through vasoconstriction. This decreases flow rates allows more time for water and sodium reabsorption in the nephrons
What is a trigger for the juxtaglomerular cells to secrete renin?
When circulating blood volume/pressure is reduced or sodium levels are low, the kidney juxtaglomerular cells release renin
How is Angiotensin II made?
renin stimulates formation of angiotensin I, which then is converted to angiotensin II by the ACE enzyme (angiotensin-converting-enzyme)
What does Angiotensin II do?
Angiotensin II stimulates release of aldosterone and ADH, and causes vasoconstriction
What is aldosterone?
mineralcorticoid
Where is aldosterone secreted from
adrenal cortex
What does aldoesterone do
Aldosterone causes renal sodium and water reabsorption
Blood volume and sodium levels are very high in the body. What peptides do you expect to be releases?
natriuretic peptides (anp, bnp)
What do ANP and BNP cause?
Cause vasodilation and increased sodium and water excretion
Where do ANP and BNP come from
ventricles
What is ADH? Where is it secreted from?
Antidiuretic Hormone, posterior pituitary gland
Describe the process of ADH secretion and what is causes
Hypothalamic osmoreceptors detect when plasma osmolality increases or when circulating blood volume/BP decreases.
In response to this the brain sends thirst signals and also the posterior pituitary gland releases ADH
Thirst signals stimulate drinking
ADH increases water reabsorption in the distal tubules and collecting ducts
What is normal K+ range in the serum
3.5-5 mmol/L
Is K+ filtered by the kidney?
ya
Where does 90% of K+ reabsorption occur in the kidney?
proximal tubule
Describe the NaK pump
Sodium-Potassium adenosine-triphosphatase active transport system (Na+- K+ATPase Pump) maintains the concentration differences and moves K+ from ICF to ECF with the help of ATP (ATP open the channels)
What promotes K+ shift INTO cells
Insulin, epinephrine, and Alkalosis promote K+ shift into cells
What promotes K+ shift OUT of cells
Exercises, cell lysis, hyperosmolality and acidosis promote K+ shift out of the cells
What part of the nephron determines amount of K+ excretion?
distal tubule
What factors influence K+ concentration and excretion
Increase in plasma K+ (e.g. through increased dietary intake) causes K+ excretion in urine
Rate of filtrate flow also affects K+ concentration, high flow (e.g due to diuretics) causes K+ excretion into urine
Changes in PH:
- Acidosis: K+ shifts to ECF. Decreased K+ levels in ICF result in decreased secretion of K+ by the tubule (contributing to Hyperkalemia)
- Alkalosis: K+ shifts into ICF, tubular also increase K+ secretion (contributing to Hypokalemia)
Aldosterone:
increase reabsorption of Na and H2O and therefore increased K+ secretion. More K+ gets excreted in urine
also increases K+ secretion through sweat glands
increases the amount of Na+ and K+ pumps available (= increased movement of K and Na in and out of cells)
Increase in plasma K+ causes K+ ____________ (excretion/ reabsorption)
excreteion
High rate of filtration (i.e., caused by diuretics) causes K+ ____________ (excretion/ reabsorption)
excretion
How does acidosis contribute to hyperkalemia?
- Acidosis: K+ shifts to ECF. Decreased K+ levels in ICF result in decreased secretion of K+ by the tubule (contributing to Hyperkalemia)
How does alkalosis contribute to hypokalemia?
- Alkalosis: K+ shifts into ICF, tubular also increase K+ secretion (contributing to Hypokalemia)
Does aldosterone cause K+ reabsorption or excretion?
increase reabsorption of Na and H2O and therefore increased K+ secretion. More K+ gets excreted in urine
also increases K+ secretion through sweat glands
increases the amount of Na+ and K+ pumps available (= increased movement of K and Na in and out of cells)
Describe symptoms of hypokalemia
Lethargy, fatigue, confusion
Nausea & vomiting
Decreased bowel sounds; distention; ileus; constipation
Thirst; inability to concentrate urine
Weakness
Flaccid paralysis
Respiratory arrest
Bladder distention
Describe symptoms of hyperkalemia
Restlessness/Irritability/Anxiety
Nausea & vomiting
GI cramps; Diarrhea
Tingling; numbness
Early: hyperactive muscles
Late: weakness & flaccid paralysis
Muscle weakness (difficult to walk)
Loss of muscle tone
Paralysis
Describe ECG changes in hypokalemia
Flattened T wave
Prolonged QT interval
ST depression
Peaked P wave
U waves present
What dysrhythmias do you see in hypokalemia
Dysrhythmia
Sinus bradycardia
Atrioventricular block
Paroxysmal atrial tachycardia.
Describe ECG changes in hyperkalemia
Peaked T wave
Shortened QT interval
ST depression
Absent P wave
Widened QRS complex
Prolonged PR interval
What dysrhythmias would you expect with hyperkalemia
Dysrhythmia
Bradycardia
Delayed conduction rhythms
Ventricular fibrillation
Cardiac arrest
A renal patient presents with restlessness, diarrhea, tingling, and hyperactive muscles. Their EC shows peaked T waves. What electrolyte disturbance are they likely experiencing?
hyperkalemia
A patient has been vomiting for 4 days with poor po intake. They are lethargic and fatigued. Their ECG shoes U waves and a flattened t wave. What electrolyte abnormality are they likely experiencing?
hypokalemia
