EXAM 3- RENAL SYSTEM Flashcards
Most of the absorption takes place in the
Proximal tubule
Electrolyte homeostasis
Na+ K+ Ca2+ Cl- HPO4
Regulation of blood pH
Removes H+from blood maintains bicarbonate ions (HCO3-) in blood
Regulation of Blood Volume/Blood Pressure
Retention of water = increases BP Elimination of water = decreases BP
Osmoregulation art ______mOsm/L
at 300 mOsm/L
Hormones Produced by the Kidney Calcitriol - Renin – Blood pressure regulation
form of Vitamin D and calcium homeostasis
Hormones Produced by the Kidney Erythropoietin responsible for
RBC production
Hormones produced by kidney Renin –
Blood pressure regulation
Excretion of Wastes
Ammonia & Urea (protein metabolism)
Arthritis known as Gout –
excess uric acid
Kidney role Performs gluconeogenesis:
Synthesis of glucose from amino
Superficial cortical nephrons:
Make up 85% of all nephrons, which extend partially into the medulla.
Juxtamedullary nephrons: Where it lies and importance?
Lie close to and extend deep into the medulla and are important for the process of concentrating urine; secrete renin.
Afferent arteriole
Bring blood toward kidney
Explain Glomerular filtration:
Water & small solutes in blood plasma move across the wall of the glomerular capillaries into glomerular capsule and then renal tubules (PCT –> loop of Henle –> DCT –> Collecting duct)
Explain Tubular reabsorption:
As “filtrate” moves along tubule water and many useful solutes reabsorbed = returned to blood
Explain Tubular secretion:
“filtrate” moves along tubule other molecules (wastes, drugs, & excess ions) are secreted into fluid
Any solutes that remain in the fluid that drains into the renal pelvis are
excreted as urine
Brush border villi role
for reabsorption
H2O absorption occur at the
thin ascending limb of henle
Electrolytes reabsorbed in the thick ascending loop of limb ratio
Na+ K+ Cl- reabsorbtion
Distal convoluted tubule : hormone and action
PTH stim.s reabsorption of Ca++
Intercalated cell function
Regulation of pH via H+ & HCO3-
Principal cell secretes
ADH & Aldosterone
Majority reabsorption of Na occur in the
Proximal tubule
What is reabsorbed in the proximal tubule
Na, Glucose, potassium Amino acid, bicarb, phosphate Urea and water (ADH not required)
Secretion in proximal tubule
H+ Foreign substance
Tonicity of the fluid in the proximal tubule
ISOTONIC
LOOP of HENLE (CADU)
Concentration of urine (countercurrent mechanism) Ascending loop sodium reabsorbed (active transport water stays in ) Descending loop water reabsorption Na+ diffuse in Urea secretion in thin segment
Tonicity of loop of henle fluid
Isotonic Hypotonic hypertonic
Distal Tubule Reabsorption of which electrolyte
Na+ H2O (ADH required) HCO3
Secretion of distal tubule (KUHNS)
K+ Urea H+ NH3 Some drugs
Tonicity of distal tubule
Isotonic or hypotonic
Collecting duct reabsorption
H2O (ADH required)
Collecting duct reabsorption or secretion of NKHN
Na K+ H+ NH3
Collecting duct there is
Urea absorption in the medulla
Tonicity of collecting duct
Final concentration
Nephron must reabsorb ______of the filtrate (as a result: ______of urine per day)
99% ‘ 1-2 Liters
______with _______Does most of the reabsorption (remainder of nephron fine-tunes)
PCT; microvilli
In PCT, Solutes are reabsorbed by both _____And ____
active transport and passive diffusion
In PCT, _______amino acids, urea and ions (Na+, K+, Ca2+, Cl-, bicarbonate, phosphate)
Glucose
In PCT, 65% of water follows by
osmosis
** 100% of_____ , -_______________GALWO are reabsorbed in the first half of the **____
Glucose, amino acids, lactic acid, water-soluble vitamins, and other nutrients PCT
Reabsorption of Na+ produces an electrical gradient that
caused Cl- to follow by passive transport
Accumulation of NaCl outside of tubule produces an osmotic gradient:
• Helps “pull” water out of tubule
Desending Limb of Loop of Henle:
– 15% of the filtered water is reabsorbed in the descending limb – High solute content of the medulla “pulls” water out – Low permeability to solutes = little reabsorption of solutes
Asending Limb of Loop of Henle:
– Variety of transporters reclaim more Na+, Cl-, & K+ ions and other ions by diffusion – Thin, ascending segment: Is more permeable to solutes and almost impermeable to water. – Thick portion of the ascending segment: Is highly permeable to sodium, potassium, and chloride and significantly less permeable to water and urea.
DCT: .
– Moderately permeable to solutes but absorbs about 15% of water – reabsorption of Na+ and Cl- continues – 15% of water reabsorption by osmosis
– The DCT serves as the major site where
parathyroid hormone stimulates reabsorption of Ca+2
*By end of DCT,
95% of solutes & water have been reabsorbed **
Collecting duct contains ________and ________makes final adjustments
Intercalated and Principal cells
Principal cells:
• Target of 2 hormones that promote reabsorption of more water and ions
ADH role
increases water reabsorption (retention)
Aldosterone @
collecting duct:
Aldosterone role
increases reabsorption of Na+ and Cl- Therefore water will also be reabsorbed!
Secretion of K+ (adjust for dietary intake of K+) done by
Aldosterone
Intercalated cells role
help regulate pH of body fluids • Proton pumps (H+ATPases)secrete protons(H+) into tubule • Reabsorb bicarbonate ions(buffers blood pH)
Tubular secretion:
– Transfer of materials from blood into filtrate/urine
Major stimuli that trigger release of Angiotensin II
Low blood volume, or BP, stimulates renin-induced production of angiotensin II
Major stimuli that trigger release of Aldosterone
Increased angiotensin II level, and increased plasma levels of K+ promote release of aldosterone by adrenal cortex.
Major stimuli that trigger release of Vasopressin (ADH)
increased osmolarity of ECF or decrease BV, promotes release of ADH from the posterior pituitary gland
Major stimuli that trigger release of ANP
Stretching of atria of heart stimulates secretion of ANP
Major stimuli that trigger release of PTH
Decreased level of plasma Ca2+ promotes release of PTH from parathyroid glands
Mechanism and site of action of Angiotensin II
Stimulates activity of Na+/H+ antiporters in PCT cells
Mechanism and site of action of Aldosterone
Enhances activity of Na-K+ potassium pump in basolateral membrane and Na+ channels in apical membrane of principals in collecting duct.
Mechanism and site of action of ADH (vasopressin) Stimulates _______Of_________into the _________of _______in _______
Stimulates insertion of water channel proteins (AQUAPORIN-2) into the apical membrane of principal cells In COLLECTING duct
Mechanism and site of action of ANP
Suppresses reabsorption of NA and water in proximal tubule and collecting duct; also inhibits secretion of ALDOSTERONE and ADH
Mechanism and site of action of PTH
Stimulates opening of Ca2+ channels in apical membrane of early distal tubule cells
Angiotensin Hormone effects
Increases reabsorption of Na and other solutes, and water which increases BV
Aldosterone Hormone effects
Increases secretion of K+ and reabsorption of Na+, Cl-, increases reabsorption of water , which increases BV
ADH Hormone effects
Increases facultative reabsorption of water , which decreases osmolarity of body fluids
ANP Hormone effects
Increases excretion of Na in URINE (NATRIURESIS); increases urine output (DIURESIS) and thus DECREASES BV
PTH Hormone effects
Increase reabsorption of Ca2+
Filtration: Average adult male rate is_____ ml/min and female is____ ml/min
125; 105
What drives filtration
BP
____Liters/day in males; ____Liters/day in females
180; 150
Glomerulus is a
Set of fenestrated capillaries
Glomerulus is supplied by the ______And drained by _______
afferent arteriole and drained by the efferent arteriole
Bowman’s (glomerular) capsule
• Circular space between visceral and parietal epithelium
Mesangial cells
support the glomerular capillaries and respond to ANP to regulate glomerular capillary flow.
Glomerular endothelial cells
• Synthesize nitric oxide (a vasodilator). • Synthesize endothelin-1 (a vasoconstrictor). • Regulate glomerular blood flow.
Visceral epithelium of the Bowman capsule • Is composed of cells called_____ are______ forms ________called _______ they modulate_____
podocytes. o Are footlike processes. o Form an elaborate network of intercellular clefts called filtration slits; modulate filtration.
Water, Ions, small molecules & small proteins move through the membrane and become
“primary urine” or “filtrate”
Blood cells, large/medium sized proteins
cannot normally be filtered
Fenestration of glomerular endothelial cells prevents
filtration of blood cells but allows all components of blood plasma to pass
Basal lamina of glomerulus prevents what?
filtration of larger proteins
Slit membrane between ________ prevents
Pedicels, prevent filtration of medium-sized proteins
Control of renal blood flow (RBF), glomerular filtration, and renin secretion occurs at this site.
JUXTAGLOMERULAR APPARATUS
Juxtaglomerular cells located where?
These specialized cells are located around the afferent arteriole where the afferent arteriole enters the glomerulus.
Mesangial cells
specialized contractile cells that support glomerulus and help regulate glomerular blood flow; and remove macromolecules from filtration
Macula densa is a portion of _________Tubule with Specialized _______And ________ cells located where?
Portion of the distal convoluted tubule with specialized sodium and chloride sensing cells is located between the afferent and efferent arterioles.
Macula Densa cells detect what?
o Detect high flitrate rate in the DCT which results in a decrease of nitric oxide and vasoconstriction in the afferent arterioles.
Kidneys receive of______to______ blood (____of CO).
1000 to 1200 ml/min ; 20-25%
_____ to ______ml as plasma (renal plasma flow [RPF])
600 to 700
Glomerular filtration rate (GFR) • _______of the RPF (120 to 140 ml/min) is filtered into
20%; Bowman’s space
GFR is Directly related to the
perfusion pressure in the glomerular capillaries
• If mean arterial pressure decreases or vascular resistance increases, then
the RBF decreases.
FF = Filtration Fraction FF =
GFR/RPF
GFR is regulated by 3 mechanisms:
– autoregulatory – neural – hormonal
Myogenic mechanism (pressure/stretch) If arterial pressure increases, stretch of the afferent arterioles_______, smooth muscle______ to _________ (aff/eeff) arteriole and perfusion
increases; contracts ; constrict afferent ;decreases.
Myogenic mechanism If arterial pressure declines, stretch of the afferent arterioles_______, smooth muscle ______ to_______ (eff/afferent)arteriole and perfusion_______
decreases; relaxes to dilate afferent; increases.
Tubuloglomerular feedback (sodium chloride content) • If sodium filtration increases, GFR_______ – Macula densa cells stimulate afferent arteriolar_______ • If sodium filtration decreases, the opposite occurs—GFR
decreases; vasoconstriction; increases
Sympathetic nervous system • Sympathetic stimulation of ______via _______receptors causes vasoconstriction, (GFR)________
afferent arterioles alpha-1 (α-1); decreases
Inhibition of Sympathetic nerves causes_____. GFR ____
Vasodilation; increases
Severe hypoxia: Stimulation of chemoreceptors • Decreases RBF by means of__________
sympathetic stimulation
RAAS role
Renin-angiotensin-aldosterone system (RAAS) Increases systemic arterial pressure, and increases sodium reabsorption
• Renin: stored and formed where ?
Enzyme is formed and stored in afferent arterioles of the juxtaglomerular apparatus
Explain RAAS mechanism
• Renin helps form angiotensin I (physiologically inactive). • In the presence of angiotensin-converting enzyme (ACE), angiotensin I is converted to angiotensin II.
Stimulates the secretion of aldosterone by the adrenal cortex.
Angiotensin II
Angiotensin II is a potent vasoconstrictor. constricts both ______and ______with greater affect on______arteriole
afferent & efferent arterioles in kidney; efferent arteriole
____________is secreted from myocardial cells in the atria
Atrial natriuretic peptide (ANP)
Stimulates antidiuretic hormone (ADH) secretion and thirst.
Angiotensin II
ANP and BNP on sodium and water
• Inhibit sodium and water reabsorption by kidney tubules.
ANP and BNP on renin and aldosterone
Inhibit secretion of renin and aldosterone.
ANP and BNP on kidney arterioles Which one they constrict, which one gets dilated
Vasodilate the afferent arterioles; constrict the efferent arterioles.
ANP and BNP on UO, BV, BP, and sodium and H2O
Increase urine output, leading to decreased blood volume and blood pressure; promote sodium and water loss.
_____________is secreted from myocardial cells in the ventricles
Brain natriuretic peptide (BNP)
Major stimulus to MYOGENIC MECHANISM
Increased stretching of smooth muscle fibers in afferent arterioles walls due to increase BP
Mechanism and site of action: MYOGENIC MECHANISM
Stretched smooth muscle fibers contract, thereby narrowing the lumen of the AFFERENT ARTERIOLES
Major stimulus to TUBULOGLOMRULAR FEEDBACK
Rapid delivery Na+ and Cl- to the macula densa due to high SBP
Mechanism and site of action TUBULOGLOMERULAR FEEDBACK
Decrease release of NO by the juxtaglomerula apparatus causes constriction of the AFFERENT ARTERIOLES
Major stimulus to NEURAL REGULATION
Increase in level of activity of RENAL sympathetic nerves releases NE.
Mechanism and site of action NEURAL REGULATION
Constriction of AFFERENT ARTERIOLES through activation of Alpha 1 receptors and INCREASED RELEASE of RENIN
HORMONE Regulation : ANGIONTENSIN II Major stimulus
Decrease BP and BV, stimulates production of angiotensin II
HORMONE Regulation : ANGIONTENSIN II Mechanism of site of action
Constriction of both afferent and efferent arterioles
HORMONE Regulation :ANP Mechanism of site of action
Relaxation of mesangial cells in glomerulus increases capillary surface area available for filtration
HORMONE Regulation :ANP Major Stimulus
Stretching of the atria of the heart stimulates secretion of ANP
Effect of Angiotensin II on GFR
Increase
Effect of ANP on GFR
Increase
Regulations that increases GFR are
Myogenic Mechanims Tubuloglomerular feedback Neural regulation
Too large to pass through capillary fenestration
Albumin
Albuminemia is caused by
injury or disease, increase BP and irritation of kidney cells lead to increase permeability
Indicates DM
Glucosuria
As a result of kidney irritation from kidney stones
Hematuria
Indicates anorexia, Starvation, too little carb in diet
Ketonuria
Tiny masses of material that have hardened and assumed the shape of the lumen of the tubule
CASTs
Specific infections in the urinary tract
Microbes
What is renal clearance
How much of a substance can be cleared from the blood by the kidneys during a given unit of time.
Permits an indirect measure of GFR
Renal clearance
GFR is the
best estimate for the functioning of renal tissue
Inulin (a fructose polysaccharide) is often used – All inulin filtered is
excreted in urine (requires constant infusion to maintain stable plasma level)
Creatinine:
Provides a good estimate of GFR since only a small amount enters urine.
Is a poor measure of GFR.
BUN
Is most valuable for monitoring the progress of chronic rather thannacute renal disease.
Plasma creatinine concentration
Clearance is used to determine renal plasma flow and blood flow
Para-Aminohippuric acid
Prerenal caused by
inadequate renal perfusion
Intrarenal caused by
injury or damage to renal parenchyma
Postrenal caused by
acute obstruction to the outflow of urine
Inflammation of the glomerulus leads to _____-and -_____
Increased permeability & dysfunction:
Nephrotic syndrome is associated with
proteinuria
Nephritic syndrome is associated with______and ____
proteinuria & hematuria
Urine protein normally:
60-100 mg/day
Nephrotic Syndrome protein per day
> 3.5 g/day =
Nephrotic syndrome is characterized by (MAH)
• massive Proteinuria • Hypoalbuminemia • Anasarca – Usually begins in the face
In nephrotic syndrome there is Hyperlipidemia why?
Liver increases lipoprotein production in response to low plasma proteins
In nephrotic syndrome there is Hyponatremia (dilutional)
Occurs with low fractional sodium excretion
In nephrotic syndrome there is Thrombophilia
Due to loss of Antithrombin III in the urine
Nephrotic syndrome classified as
Primary glomerulonephritis Secondary glomerulonephritis
Primary glomerulonephritis: MFMM
– Minimal change disease (MCD) – Focal segmental glomerulosclerosis (FSGS) – Membranous glomerulonephritis (MGN) – Membranoproliferative glomerulonephritis (MPGN)
Minimal change disease (MCD) is most common cause of nephrotic syndrome in
Children
Causes MCD • Tx: ______
Lithium NSAIDs, CA, Infx. Steroids
Focal segmental glomerulosclerosis (FSGS) • Most common cause of nephrotic syndrome in
adults
Causes of Focal segment Glomerulosclerosis (MUPTHH)
- unilateral renal agenesis – morbid obesity – previous kidney injury – Toxins – HIV – Heroine
Tx of Focal segment Glomerulosclerosis
ACEI, Diuretics, salt restriction
Antibodies bind to antigens in basement membrane
Membranous glomerulonephritis (MGN)
Causes of Membranous glomerulonephritis :
SLE, Hep B,C, NSAIDs, Gold, Mercury
Tx of Membranous glomerulonephritis
Immune suppressors (Cyclophosphamide) & steroids
in MGN Immune complexes trigger
MAC of complement system
Membranoproliferative glomerulonephritis Causes
Auto-immune ds., Hep B, C, cryoglobulinemia, SBE
Membranoproliferative glomerulonephritis Type I
Discrete immune complexes are found in the mesangium and subendothelial space.
Membranoproliferative glomerulonephritis Type II
also called dense deposit disease. Continuous, dense ribbon-like deposits found along basement membranes of the glomeruli, tubules, & Bowman’s capsule
NEPHROTIC SYNDROME CAUSES Diabetic nephropathy
– SLE – Sarcoidosis – Syphilis – Hepatitis B – Sjögren’s syndrome – HIV – Amyloidosis – Multiple myeloma – Vasculitis – Cancer – Genetic disorders – Drugs
IgA Nephropathy
Most common cause of Nephritic Syndrome worldwide Abnormal IgA binds to mesangium of glomerulus activating complement MAC damaging vessel wall
• “Cola” colored hematuria
IgA Nephropathy
Treatment of Iga Nephropathy
Steroids – ACEi – (Immunosuppressives) • Cyclophosphamide – onlyin recurrent episodes
Post-streptococcal glomerulonephritis
Anti-streptococcal antibodies – antigen-antibody complexes deposit in glomeruli – Activate complement MAC = vessel damage – Increased capillary permeability – leakage of protein and large numbers of erythrocytes
Treatment of post streptococcal glomerulonephritis
BP meds, Diuretics, ABX if needed
Triad of Hemolytic Uremic syndrome
Triad of Hemolytic anemia, ARF & Thrombocytopenia
Often preceded by food poisoning
Hemolytic uremic syndrome
In Hemolytic Uremic syndrome, bacterial toxins ___
Bacterial toxins bind to glomerular endothelium – trigger apoptosis & binding of leukocytes
Hemolytic Uremic syndrome tx
• Tx: ABX & hemodialysis prn
Henoch–Schönlein purpura aka
IgA vasculitis, self limiting
Treatment of Henoch–Schönlein purpura
same as nephropathy IgA (Steroids, ACEI, immunosuppressive)
What is good pasture syndrome
Attack basement membrane of kidney and lung
Tx of good pasture syndrome
treatment w/ monoclonal antibodies
SLE
Autoantibodies attack mesangial cells of juxtaglomerular apparatus leading to lupus nephritis
• Tx of SLE
steroids, antimalarials, cyclophosphamide
Assoc’d. with Goodpasture’s Syndrome or SLE
Rapidly progressing glomerulonephritis
Rapidly progressing Glomerulonephritis there is rapid loss of
Rapid loss of renal function: 50% decline in GFR within 3 months
• ANCA (antineutrophil cytoplasmic antibodies) causes an early degranulation
Rapidly progressing glomerulonephritis
Tx of Rapidly progressing glomerulonephritis
Tx: steroids, cyclophosphamide, plasmapheresis
Release of lytic enzymes damage glomerulus • Causes glomerular crescent formation
Rapidly progressing glomerulonephritis
Inflammation of tissue between renal tubules
Interstitial Nephritis
Causes of Interstitial Nephritis Allergic reaction to medications
RPPP - CNSQ Rifampin Phenytoin PCN PPIs Cephalosporins NSAIDs Sufanemides Quinolones
Infection that can cause Interstitial Nephritis
• pyelonephritis
Blood Tests of interstitial nephritis – ~25% of pts. have
eosinophila
UA for interstitial nephritis shows
– Hematuria, Proteinuria – Sterile Pyuria – Eosinophila
– Gallium-67 scan
60%-100% positive
Tx of interstitial nephritis
Treat underlying cause
First manifestation of PKD
around 40
S/S of PKD
HHHPE (HTN, HA, Pain, Excessive urination, Hematuria)
Rhabdomyolysis
Damaged skeletal muscle leaks myoglobin into the circulation.
Myoglobin interacts with
interacts with Tamm–Horsfall protein in the nephron to form casts that obstruct flow.
In rhabdomyolosis, Fe from ____
Fe++ from heme generates reactive oxygen species which damages the kidney cells
Blood tests in Rhabdo
Blood Tests: – Increased CK – Increased LDH – Hyperkalemia
Fanconi syndrome
Dysfunction of the proximal tubules – multichannel transport failure results in excretion of most solutes
In fanconi syndrome_____Excretion of ____
Increased excretion of bicarb. = Renal Tubular Acidosis (RTA)
Electrolyte disturbances in Fanconi syndrome
Hypokalemia Hypophosphatemia
Hypophosphatemia can result in bone diseases
– Rickets, Osteomalacia
TX of Fanconi syndrome
• Tx: fluid & electrolyte replacement
In fanconi syndrome Hypokalemia occurs b/c
large load of filtered solute reaching distal nephron stim.s K+ excretion (similar to action of loop & thiazide diuretics)
TUMOR LYSIS syndrome is when
CA cells killed during treatment release their contents into bloodstream: K+, Phosphorus, Uric acid (nucleics)
Electrolytes abnormalities in Tumor Lysis syndrome
Hyperkalemia • Hyperphosphatemia / Hypocalcemia • Hyperuricemia • ELEVATED BUN
In TLS, Hyperphosphatemia causes________Secondary to deposition of
acute kidney failure 2 ; calcium phosphate crystals in the kidney parenchyma.
In TLS , Hyperuricosuria -
uric acid crystals obstruct tubules
Acute Tubular Necrosis Classified as_____ or ___
• Classified as Toxic or Ischemic
Tx of TLS
Hemodialysis
Color of casts in ATN
Muddy brown casts
Treatment of ATN
Tx: underlying cause – Hydration – Stop offending drug
Toxic ATN involves ______only
PCT
Drugs that cause ATN
CRA (Cisplastin, Aminoglycosides, Radiographic contrast) MASEH – Methotrexate – Amphotericin B – Statins – Ethylene glycol – Heavy metals
Ischemic ATN characterized by________
Patchy PCT & DCT necrosis
Ischemic ATN Caused by
prolonged hypotension (Hypovolemia, Shock)
PCT and ascending thick limb require increase ATP for nutrient and electrolyte reabsorption
highly susceptible to ischemic damage
Identify the parts
A- Filtration
B- Pedicel
Identify A and B
A- Neutrophils
B- Hump-like Subendothelial cells
Immune Complex deposits
Identify A and B
A- Normal Glomerulus (normal podocytes)
B- Glomerulus affected by minimal changes (damaged podocytes)
What is this disorder?
Henoch–Schönlein purpura • a.k.a. “IgA Vasculitis”
