Renal Physiology 1 Flashcards
What separates hte intracellular and extracellur fluid?
cell membrane
bilipid layer
proteins
cell membrane
Cell membrane component taht controls the entry of fluid and electrolyte
cell membrane
bilipid layer
proteins
bilipid layer
Cell membrane component taht acts as channels or transporters
cell membrane
bilipid layer
proteins
proteins
part of fluid compartment that :
- in between cells
- fluid in blood vessels
- in specific places like CSF, synovial joint , plueral
Intracellular Extracellular Intravascular Interstitila Trans cellular
Interstitial
Intravascular
Trans cellular
All other blood vessels have no movement of fluid except at the capillaries. Why?
Movement of fluid is only at the level of capillary, because it has at least 3 layers
Movement of fluid and other electrolytes are limited to capillaries where blood exchange happens by the process of diffusion
Capillaries are also known as interstitial exchanger
Capillaries also have pores and gaps which determine what can pass and what can’t
Capillaries also have pores and gaps which determine what can pass and what can’t
Movement of fluid is only at the level of capillary, because it has a single layer only, in contrast with other blood vessels which have at least 3 layers
Movement of fluid and other electrolytes are limited to capillaries where blood exchange happens by the process of diffusion
Capillaries are also known as exchange vessels
To measure total body water:
= use substance that will stay in the blood vessel and will not go out through the pores of the capillary (radioactive albumin) or a substance that binds proteins (Evans blue dye)
= use radioactive water or heavy water
= plasma/ 1 – hematocrit
= Uses inulin and radioactive Na or Cl
= causes differential distribution of ions due to the Na-K pump which makes the sodium goes out, because where the Na goes H2O will follow
= material that will pass through the blood compartment into the interstitial space but not pass through the cell membrane
Extracellular volume Inulin Radioactive Na or Cl Intracellular volume = TBW-ECF ; it can only be estimated Plasma Total blood volume Total body water
To measure total body water:
Total body water = use radioactive water or heavy water
Extracellular volume
o use inulin – material that will pass through the blood compartment into the interstitial space but not pass through the cell membrane
o Radioactive Na or Cl – causes differential distribution of ions due to the Na-K pump which makes the sodium goes out, because where the Na goes H2O will follow
Intracellular volume = TBW-ECF ; it can only be estimated
Plasma = use substance that will stay in the blood vessel and will not go out through the pores of the capillary (radioactive albumin) or a substance that binds proteins (Evans blue dye)
Total blood volume = plasma/ 1 – hematocrit
Movement of fluid across vascular endothelium and cell membrane
Cell membrane Na+K+ATPAse ____
___ is determined by Na+
Most cells are permeable to water which moves by ___
Osmolarity of ___
K+ intracellular Na+ extracellular intracellular fluid ECF volume osmosis
Movement of fluid across vascular endothelium and cell membrane
Cell membrane Na+K+ATPAse = K+ intracellular and Na+ extracellular
ECF volume is determined by Na+
Most cells are permeable to water which moves by osmosis
Osmolarity of intracellular fluid
- ____determines what’s in intravascular space vs.
interstitial space. - The movement of Na and Cl across the capillary is
based on ____ - H2O will also move via ___
- ____ that attracts H2O and depends on solute that is not
permeable or stays in particular compartment
diffusion
osmotic pressure
osmosis
capillary
Capillary determines what’s in intravascular space vs.
interstitial space. The movement of Na and Cl across the capillary is
based on diffusion; H2O will also move via osmosis (osmotic
pressure that attracts H2O and depends on solute that is not
permeable or stays in particular compartment).
Main cation in the plasma and interstitial fluid is
___, while in the intracellular fluid it’s ___.
Na
K
Main cation in the plasma and interstitial fluid is Na, while in the intracellular fluid it’s K.
o specific material inside cells that will never pass out
o proteins in plasma that will never get into the interstitium because they are very large and cannot pass through the pores
o except when pores are made large (histamine and
bradykinin -> ___), in which case the proteins can enter and eventually will cause ___
o There should be electrolyte neutrality; the total number of
positive and negative ions on each side of the compartment
must be equal because of ____
edema Gibbs Donnan equilibrium Albumin and plasma proteins Intracellular proteins increases permeability
Intracellular proteins
o specific material inside cells that will never pass out
Albumin and plasma proteins
o proteins in plasma that will never get into the
interstitium because they are very large and cannot
pass through the pores
o except when pores are made large (histamine and
bradykinin -> increases permeability), in which case
the proteins can enter and eventually will cause
edema
There should be electrolyte neutrality; the total number of
positive and negative ions on each side of the compartment
must be equal because of Gibbs Donnan equilibrium.
- cell will not shrink nor swell
- cell will swell
- cell will shrink
- higher concentration of impermeant solutes than cell
- lower concentration of impermeant solutes
- same concentration of impermeant solutes between cell and the solution
- ## e.g. 0.9% NaCl; 5% glucose solution
Hypotonic solution
o lower concentration of impermeant solutes (
What if you give hypotonic solution?
ECF volume
ICF volume
total volume
osmolality
increase
decrease
Q: What if you give hypotonic solution?
↑ ECF volume ↑ ICF volume = ↑ total volume
↓ osmolality
What happens to the ECF volume and osmolality and ICF volume
and osmolality when you give isotonic NaCl to a patient?
Osmolality will increase
total volume would decrease (due to decrease in ECF volume)
It will not go intracellularly so ICF volume would not
change unless the person is dehydrated
What happens to the ECF volume and osmolality and ICF volume
and osmolality when you give isotonic NaCl to a patient?
Osmolality will not change
total volume would increase (due to ↑ECF volume)
It will not go intracellularly so ICF volume would not
change unless the person is dehydrated
Production and secretion of hormones
- triggered by hypoxia (↓ O2)
- released when there is low blood flow to kidneys
- RAAS (see below) – for long term regulation of BP
- regulation of Ca2+
- Hydroxylation reactions (at position 1: kidney, at position 25: liver)
o Erythropoietin
o 1,25 hydroxyvitamin D3 (calcitriol)
o Renin
Production and secretion of hormones
o Erythropoietin – triggered by hypoxia (↓ O2)
o Renin
released when there is low blood flow to kidneys
RAAS (see below) – for long term regulation of
BP
o 1,25 hydroxyvitamin D3 (calcitriol)
regulation of Ca2+
Hydroxylation reactions (at position 1: kidney, at
position 25: liver)
MAIN FUNCTION of renal system
- maintaining balance
- Regulation of body fluid volume and osmolality –it can conserve
or regulate ions and electrolytes. - Regulation of electrolyte balance
- Excretion of waste products (urea, ammonia, drugs, toxins)
- Regulation of acid-base balance
Renal system
MAIN FUNCTION: Maintaining balance
Regulation of body fluid volume and osmolality –it can conserve
or regulate ions and electrolytes.
Regulation of electrolyte balance
Excretion of waste products (urea, ammonia, drugs, toxins)
Regulation of acid-base balance
Renin Angiotensin-Aldosterone System.
A decrease in BP will result to a decreased blood flow (GFR) to the kidneys, stimulating the macula densa (sensitive to Na concentration) of the DCT. The juxtaglomerular cells will release renin.
Renin catalyzes the conversion of angiotensinogen to angiotensin I. Angiotensin I will: a) vasoconstrict blood vessels increasing the TPR resulting to an increase in BP (corrected) b) be converted to angiotensin II by ACE (Angiotensin converting enzyme) which is from the lungs. Angiotensin II is the more potent vasoconstrictor. It will also stimulate the adrenal cortex to secrete aldosterone. Aldosterone promotes Na reabsorption thereby increasing the water retention resulting to an increased BP.
Renin Angiotensin-Aldosterone System. A decrease in BP will result to a decreased blood flow (GFR) to the kidneys, stimulating the macula densa (sensitive to Na concentration) of the DCT. The juxtaglomerular cells will release renin. Renin catalyzes the conversion of angiotensinogen to angiotensin I. Angiotensin I will: a) vasoconstrict blood vessels increasing the TPR resulting to an increase in BP (corrected) b) be converted to angiotensin II by ACE (Angiotensin converting enzyme) which is from the lungs. Angiotensin II is the more potent vasoconstrictor. It will also stimulate the adrenal cortex to secrete aldosterone. Aldosterone promotes Na reabsorption thereby increasing the water retention resulting to an increased BP.
Blood Flow to the kidneys = ___ in resting person
- 0 L/min
- 25 L/min
- 0 L/min
- 5 L/min
Blood Flow to the kidneys= 1.25L/min in resting person
The osmolality of the body is maintained at approximately ____
o except in the medulla which is hyperosmolar (responsible for conservation of water)
100 mOsm 200 mOsm 300 mOsm 400 mOsm 500 mOsm
The osmolality of the body is maintained at approximately 300 mOsm
o except in the medulla which is hyperosmolar (responsible for conservation of water)
Kidney is an excellent blood supply
o it receives ___% of Cardiac Output ( ____ L/min) because its major role is to remove waste and regulate electrolyte balance
o ___% total body weight
0.5% 1% 2% 10% 20% 50%
- 0 L/min
- 25 L/min
- 0 L/min
- 5 L/min
excellent blood supply
o it receives 20% of Cardiac Output (1L/min) because its major role is to remove waste and regulate electrolyte balance
o 0.5% total body weight
Which statement is true regarding the NEPHRON
a Total of about 2.5 million in the one kidney
b. The functional unit of the liver
c .Each nephron consists of 2 functional components:
o The tubular component (contains what will eventually become urine)
o The vascular component (blood supply)
d. The mechanisms by which kidneys perform their functions depends upon the relationship between these two components
THE NEPHRON
Total of about 2.5 million in the 2 kidneys.
The functional unit of the kidney
Each nephron consists of 2 functional components:
o The tubular component (contains what will eventually become urine)
o The vascular component (blood supply)
The mechanisms by which kidneys perform their functions depends upon the relationship between these two components
___ helps regulate renal blood flow, GFR and also indirectly, modulates Na balance and systemic BP.
Golgi apparatus SER JGA Kidneys Pancreas
Juxtaglomerular apparatus (JGA). The JGA helps regulate renal blood flow, GFR and also indirectly, modulates Na balance and systemic BP.
- hollow tubes composed of a single cell layer
- made up of glomerular capillaries and Bowman’s capsule.
Nephron
Renal Corpuscle
Nephron – hollow tubes composed of a single cell layer
(renal corpuscle, proximal tubule, loop of henle, distal tubule and
collecting duct system). Renal Corpuscle – made up of glomerular
capillaries and Bowman’s capsule.
Juxtamedullary nephron is composed of ____% of all nephrons
10-20
20-30
30-40
40-50
Juxtamedullary nephron (20-30% of all nephrons)
- At the junction of cortex and medulla
- Long U shaped loop of Henle (goes into medulla)
- Short loop of Henle, does not go deep into the medulla
- Peritubular capillaries
- Eventually have tubules which end up in the collecting duct
- Peritubular capillaries and vasa recta return toward cortex and empty into the ___
Cortical nephrons Juxtamedullary nephron cortical veins hepatic veins portal veins
Juxtamedullary nephron
At the junction of cortex and medulla
Long U shaped loop of Henle (goes into medulla)
Cortical nephrons
Short loop of Henle, does not go deep into the medulla
Peritubular capillaries
Both cortical and juxtamedullary nephrons eventually have
tubules which end up in the collecting duct
Peritubular capillaries and vasa recta return toward cortex and
empty into the cortical veins
The three basic renal processes: \_\_\_\_ filtration \_\_\_\_ reabsorption \_\_\_\_ secretion Product: \_\_\_
Glomerular
Tubular
urine
The three basic renal processes: Glomerular filtration Tubular reabsorption Tubular secretion Product: urine
Juxtaglomerular cell is in the ________ arteriole
efferent
afferent
Juxtaglomerular cell is in the afferent arteriole
Glomerulus is made up of capillaries surrounded by epithelial lining called the ____
Loop of Henle
Renal Corpuscle
Glomerular barrier
Bowman’s capsule
Glomerulus is made up of capillaries surrounded by epithelial lining called the Bowman’s capsule
N.B. it is the ____ that is being regulated, NOT the urine
ECF
ICF
TBW
N.B. it is the ECF that is being regulated, NOT the urine
Plasma is filtered through the ___
Loop of Henle
Renal Corpuscle
Glomerular barrier
Bowman’s capsule
Plasma is filtered through the Glomerular barrier
- Fenestrated (has pores), freely permeable to water and small solutes and most proteins
- 50x more permeable than other capillaries
- not permeable to RBC, WBC and platelets
- retard filtration of large anionic protein into Bowman’s space
- negatively charged proteins can’t pass through (like charges repel)
- have Parietal and visceral layers
- filtration slits allow molecules with a size of s space
Podocytes
Capillary endothelium
Basement membrane
Epithelium of Bowman’s Capsule
Capillary endothelium
Fenestrated (has pores), freely permeable to water and small solutes and most proteins
50x more permeable than other capillaries
not permeable to RBC, WBC and platelets
retard filtration of large anionic protein into Bowman’s space (presence of glycoproteins [negatively charged] on surface)
o Basement membrane
net negative charge
negatively charged proteins can’t pass through (like charges repel)
o Epithelium of Bowman’s Capsule
Parietal and visceral layers
Podocytes – filtration slits allow molecules with a size of s space
the ability of a molecule to cross the membrane depends on except:
o Size (<60kD)
o Charge (should not be negative)
o Shape
o Weight
the ability of a molecule to cross the membrane depends on:
o Size (<60kD)
o Charge (should not be negative)
o Shape
– increased permeability of the glomerular capillaries to protein and loss of normal podocyte function
– hematuria and progressive glomerulonephritis, defect in type IV collagen in glomerular basement membrane.
Alport’s syndrome
Nephrotic Syndrome
Nephrotic Syndrome – increased permeability of the glomerular capillaries to protein and loss of normal podocyte function
o Alport’s syndrome – hematuria and progressive glomerulonephritis, defect in type IV collagen in glomerular basement membrane.
____ drive ultrafiltration process across glomerular capillaries
Starling’s forces
Hydrostatic force
Oncotic force
Starling’s forces – drive ultrafiltration process across glomerular capillaries (hydrostatic and oncotic forces)
Measure of functional capacity of the kidney
Normal =
120 ml/min
99% of fluid filtered is reabsorbed
1.2 ml/min
1% of fluid filtered is reabsorbed
Normal = 120 ml/min =7.2 L/h =180 L/day (99% of fluid filtered is reabsorbed)
Normal GFR, transfer blood passing through per minute there is ___ of fluid in the ultrafiltrate in the Bowman’s capsule
100 mL 125 mL 150 mL 175 mL 200 mL
Normal GFR, transfer blood passing through per minute there is 125 mL of fluid in the ultrafiltrate in the Bowman’s capsule
= blood was not able to cleaned, the kidney was unable to remove creatinine
decrease Creatinine clearance
increase Creatinine clearance
↓ Creatinine clearance = blood was not able to cleaned, the kidney was unable to remove creatinine
- Afferent arteriole dilatation: Prostaglandins, kinins, dopamine (low dose), ANP, NO/EDRF
- Efferent arteriole dilatation: Agiotensin II blockade
- Afferent arteriole constriction: Angiotensin II (high dose), Noradrenaline (sympa n), endothelin, ADH, prostaglandin blockade (mefenamic acid)
- Efferent arteriole constriction: Agiotensin II (low dose)
To ↑ GFR:
To ↓ GFR:
To ↑ GFR:
- Afferent arteriole dilatation: Prostaglandins, kinins, dopamine (low dose), ANP, NO/EDRF
- Efferent arteriole constriction: Agiotensin II (low dose)
To ↓ GFR:
- Afferent arteriole constriction: Angiotensin II (high dose), Noradrenaline (sympa n), endothelin, ADH, prostaglandin blockade (mefenamic acid)
- Efferent arteriole dilatation: Agiotensin II blockade
o glomerular capillaries, fenestrated, 50x more permeable than other capillaries
o Sialoproteins (in podocytes), negatively charged
o Pore size smaller than albumin
o contraction of mesangial cells (cell in the glomerulus which can relax/ contract) = ↓surface area for filtration – less filtration
o contraction: Angiotensin II, ADH, NE, PDGF, Thromboxane A2, platelet activating factor, Leukotiene C and D, histamine
o relaxation: ANP, dopamine, PGE2, cAMP
o factors affecting hydrostatic pressure
- Permeability
- Capillary bed size
- Hydrostatic and osmotic pressure
Permeability
o glomerular capillaries, fenestrated, 50x more permeable than other capillaries
o Sialoproteins (in podocytes), negatively charged
o Pore size smaller than albumin
Capillary bed size
o contraction of mesangial cells (cell in the glomerulus which can relax/ contract) = ↓surface area for filtration – less filtration
Hydrostatic and osmotic pressure
o factors affecting hydrostatic pressure
Causes capillary bed size relaxation?
Causes capillary bed size contraction?
Angiotensin II ADH NE PDGF Thromboxane A Leukotiene C and D Histamine ANP Dopamine PGE2 cAMP
Capillary bed size
o contraction: Angiotensin II, ADH, NE, PDGF, Thromboxane A2, platelet activating factor, Leukotiene C and D, histamine
o relaxation: ANP, dopamine, PGE2, cAMP
autoregulation of arterial pressure
sympathetic stimulation
factors affecting osmotic pressure
changes in concentration of plasma proteins
myogenic theory
bet 90-190 mm Hg the pressure is remained as constant RPF thus GFR
arteriolar resistance
↑ sympathetic activity = ↑ renin activity
autoregulation of arterial pressure
- myogenic theory
- bet 90-190 mm Hg the pressure is remained as constant RPF thus GFR
sympathetic stimulation
- arteriolar resistance
- ↑ sympathetic activity = ↑ renin activity
factors affecting osmotic pressure
changes in concentration of plasma proteins
Inc/dec
Hypotension (\_\_\_BP)
↓
\_\_ sympathetic tone
↓
Efferent and afferent arteriolar (constriction or dilation ?)
↓
\_\_ renal vascular resistance
↓
\_\_ GFRHypotension (↓BP)
↓
↑ sympathetic tone
↓
Efferent and afferent arteriolar constriction
↓
↑ renal vascular resistance
↓
↓ GFRHypertension (\_\_\_BP)
↓
\_\_\_ sympathetic tone
↓
Efferent and afferent arteriolar (constriction or dilation ?)
↓ \_\_\_ renal vascular resistance
↓
\_\_\_ GFR
Hypertension (↑BP)
↓
↓ sympathetic tone
↓
Efferent and afferent arteriolar dilation
↓
↓ renal vascular resistance
↓
↑ GFRarteriolar resistance (inc/dec)??
o afferent arteriole RPF GFR
constriction ? ?
dilation ? ?
o efferent arteriole RPF GFR
constriction ? ?
dilation ? ?
arteriolar resistance
o afferent arteriole RPF GFR
constriction ↓ ↓
dilation ↑ ↑
o efferent arteriole RPF GFR
constriction ↓ ↑
dilation ↑ ↓
Tubular Reabsorption ?
Tubular secretion ?
– from blood to lumen
– from lumen to blood
Tubular Reabsorption – from lumen to blood
Tubular secretion – from blood to lumen
Nephron segments:
Proximal convoluted tubule Descending limb of Loop of Henle Ascending limb of Loop of Henle Distal convoluted tubules Collecting duct
o “diluting segment of the nephron”
o Presence of ion pumps, it gets ions out of the tubule and brings it into interstitium against concentration gradient
o with brush border (increases SA for reabsorption)
o is permeable to water but not to solute
o Acted upon by aldosterone and ADH
o no passage for water but it has for solute.
o has a lot of transporters so when it passes through it, there will be more electrolytes that will be reabsorbed
o more water than solute
o structurally no carrier for solute
Nephron segments:
Proximal convoluted tubule
o has a lot of transporters so when it passes through it, there will be more electrolytes that will be reabsorbed
o with brush border (increases SA for reabsorption)
Descending limb of Loop of Henle
o is permeable to water but not to solute
o structurally no carrier for solute
Ascending limb of Loop of Henle
o no passage for water but it has for solute.
o Presence of ion pumps, it gets ions out of the tubule and brings it into interstitium against concentration gradient
Distal convoluted tubules
o more water than solute
o “diluting segment of the nephron”
Collecting duct
o Acted upon by aldosterone and ADH
TRUE/FALSE.
All cells in nephron, except for the intercalated cells have primary cilia – acts as mechanoreceptors (rate of flow) and chemoreceptors (respond to compounds)
True
All cells in nephron, except for the intercalated cells have primary cilia – acts as mechanoreceptors (rate of flow) and chemoreceptors (respond to compounds)
Collecting duct 2 cell types:
Principal cells
Intercalated cells
- few mitochondria
- with high density of mitochondria
- secretes H+ and HCO+
- for reabsorption of NaCl and secretion of K+
- moderately invaginated into the basolateral membrane
- for acid base balance
Collecting duct 2 cell types:
Principal cells - moderately invaginated into the basolateral membrane - few mitochondria - for reabsorption of NaCl and secretion of K+ Intercalated cells - for acid base balance - with high density of mitochondria - secretes H+ and HCO+
