Exam 4 pt. 2 Flashcards
Generally, how much filtrate is made each day? How much urine?
o ~180 L (47 gallons) of blood-derived filtrate is processed by the kidneys each day, only ~1.5L of urine is formed – less than 1%!
o The kidneys filter the body’s entire blood plasma volume 60x each day
o At rest, 20-25% of the body’s O2 supply is used by the kidneys
Define filtrate
o Filtrate: blood plasma minus its proteins; produced by glomerular filtration
Define urine
o Urine: metabolic wastes and unneeded substances; produced from filtrate
List the 3 processes involved in urine formation. What happens in each process?
o Glomerular Filtration: produces cell and protein-free filtrate
o Tubular Reabsorption: process of selectively reclaiming substances from filtrate and moving them back into blood
Typically, 99% of water, and all glucose and amino acids are reabsorbed
o Tubular Secretion: process of selectively moving substances from blood into filtrate
What are the 3 layers of the filtration membrane?
o Fenestrated Endothelium of Glomerular Capillaries: allows all blood components except cells to pass
o Basement Membrane: allows solutes; blocks all but the smallest proteins
o Foot Processes of Podocytes of the Glomerular Capsule: filtration slits between foot processes, stop all remaining macromolecules
Define the 3 pressures involved in glomerular filtration and have a general idea of their valves.
o Outward Pressures: forces that promote the formation of filtrate
o Hydrostatic Pressure in Glomerular Capillaries (HPgc) – essentially glomerular blood pressure
Chief force pushing water, solutes out of blood across the filtration membrane
Quite high (55mmHg) compared to most capillary beds
Maintained by the smaller size of efferent arteriole versus the afferent arteriole
o Inward Pressures: forces that inhibit the formation of filtrate
o Hydrostatic Pressure in the Capsular Space (HPcs) – pressure exerted by the filtrate in the glomerular capsule (~15mmHg)
o Colloid Osmotic Pressure in Glomerular Capillaries (OPgc) – the “pull” of the proteins in the blood (~30mmHg)
Define outward pressure
o Outward Pressures: forces that promote the formation of filtrate
Define hydrostatic pressure in glomerular capillaries
o Hydrostatic Pressure in Glomerular Capillaries (HPgc) – essentially glomerular blood pressure
Chief force pushing water, solutes out of blood across the filtration membrane
Quite high (55mmHg) compared to most capillary beds
Maintained by the smaller size of efferent arteriole versus the afferent arteriole
Define inward pressures
o Inward Pressures: forces that inhibit the formation of filtrate
Define hydrostatic pressure in capsular space
o Hydrostatic Pressure in the Capsular Space (HPcs) – pressure exerted by the filtrate in the glomerular capsule (~15mmHg)
Define Colloid Osmotic Pressure in Glomerular Capillaries (OPgc)
o Colloid Osmotic Pressure in Glomerular Capillaries (OPgc) – the “pull” of the proteins in the blood (~30mmHg)
Define NFP. Is it a net outward or inward force?
o Net Filtration Pressure (NFP): the sum of forces
55mHg forcing out
45mmHg forcing in
Net: 10mmHg of outward force
o NFP is the pressure responsible for forming filtrate
o NFP is the main controllable factor for determining Glomerular Filtration Rate (GFR)
What is GFR?
o GFR: the volume of filtrate formed by both kidneys per minute
o Normal GFR = 120 - 125 mL/min
How is GFR used clinically? What 3 things determine GFR?
o GFR is directly proportional to:
Net Filtration Pressure (NFP): main controllable factor, primary pressure is outward glomerular hydrostatic pressure, can be controlled by changing arteriole diameters
Total surface area available for filtration – controlled by the contraction of mesangial cells
Permeability of filtration membrane – much more permeable than other types of capillaries
o Large surface area and high permeability allow the relatively small NFP to produce huge amounts of filtrate
In terms of GFR, what is normal for a healthy adult? What values are associated with CKD? With renal failure?
Describe the relationship between GFR and systemic blood pressure.
o GFR is regulated to serve 2 important – and sometimes opposing – needs
o The kidneys need a relatively constant GFR to continue making filtrate
o The body needs a relatively constant blood pressure
o An increase in GFR increases urinary output and decreases BP
o A decrease in GFR decreases urinary output and increases BP
What’s the difference between intrinsic and extrinsic controls?
o Intrinsic Controls: work locally within the kidney to maintain GFR – renal autoregulation
o Extrinsic Controls: neural and hormonal controls that maintain systemic blood pressure
What is an appropriate MAP range for intrinsic controls to be in control?
o 80-180 mmHg
Define myogenic mechanism. What happens when BP increases or decreases under myogenic mechanism?
o Myogenic Mechanism: smooth muscle contracts when stretched
Increased BP -> Muscles Stretch -> Constriction of Afferent Arteriole
Decreased BP -> Dilation of Afferent Arteriole
Goals: protect the glomerulus from high BP by restricting blood flow, maintain normal NFP and GFR
Define tubuloglomerular feedback mechanism. What group of cells directs this mechanism? What solute is driving this mechanism?
o Tubuloglomerular Feedback Mechanism: directed by the macula densa cells
Responds to NaCl concentration
GFR increases -> flow of filtrate increases -> decreased time for reabsorption -> higher levels of NaCl in filtrate
Response: the afferent arteriole is constricted -> NFP and GFR are reduced -> increased time for NaCl reabsorption
What systemic effects are seen in extrinsic neural control by the SNS? How does this alter BP?
o Extrinsic controls regulate GFR to maintain systemic BP – even if it hurts the kidneys!
o Ex: in the event of hypovolemia, extrinsic controls will override the intrinsic controls to ensure survival of the vital organs
o Neural Control by the Sympathetic Nervous System
Normal Conditions: renal blood vessels are dilated, intrinsic controls running
Abnormal Conditions (Low BP): norepinephrine, epinephrine are released
* Systemic vasoconstriction to raise BP
* Constriction of the afferent arterioles will decrease GFR
* Blood volume and blood pressure increase
Outline how renin increases systemic blood pressure.
o Renin-Angiotensin-Aldosterone Mechanism
o The body’s main mechanism for increasing blood pressure
o 3 pathways to releasing renin from the granular cells
Direct stimulation of granular cells by the SNS
Simulation of the granular cells by activated macula densa cells – when NaCl concentration in filtrate is low
Reduced stretch of granular cells
o Anuria: abnormally low urine output (< 50 mL/day); multiple causes
What are some things that are reabsorbed in tubular reabsorption? Which portion of the renal tubule conducts the most reabsorption?
o Tubular reabsorption quickly reclaims most of the tubular contents and returns them to blood
o Tubular reabsorption is an elective transepithelial process. It starts as soon as filtrate enters the proximal tubule.
o Almost all organic nutrients are reabsorbed; reabsorption of water and ions is hormonally regulated and adjusted as needed
o Tubular reabsorption can be either active (ATP-requiring) or passive
o Two Routes:
Transcellular: reabsorbed substances travel through cells of the tubule
Paracellular: reabsorbed substances travel between cells of the tubule
What is reabsorbed in the PCT?
The PCT is the site of most reabsorption
What is reabsorbed from the filtrate in the PCT?
* All the nutrients (glucose + amino acids)
* 65% of sodium + water
* Most of the electrolytes
* Nearly all uric acid and ~1/2 of the urea – these will be secreted into the filtrate again later!
What is reabsorbed in the Nephron Loop?
In the nephron loop, reabsorption of water is no longer coupled to solute reabsorption
Descending Limb: water can leave, but solute cannot
Ascending Limb: solute can leave, but water cannot
What is reabsorbed in DCT?
Reabsorption in the DCT varies with the body’s current needs – it is hormonally regulated
Most of the water and solutes have already been reabsorbed
Anti-Diuretic Hormone (ADH): released by the posterior pituitary gland, can cause an increase in reabsorption of water
Aldosterone: increases blood pressure and decreases K+ levels by promoting the reabsorption of Na+
Atrial Natriuretic Peptide (ANP): released by cardiac atrial cells, decreases blood volume and blood pressure by reducing the reabsorption of Na+
Parathyroid Hormone: increases reabsorption of Ca2+ by the DCT
Refamiliarize yourself with ADH, aldosterone, ANP, and parathyroid hormone. What do each of these do?
What is tubular secretion? Make a list of things typically secreted.
o Tubular secretion is the reverse of tubular reabsorption
o Tubular secretion occurs almost entirely in the PCT
o In secretion, selected substances are moved from the peritubular capillaries, through the tubule cells, and back into the filtrate
o Things that are often secreted: K+, H+, Ammonia, Creatinine, Organic Acids and Bases
o Tubular secretion is important for:
Disposing of substances – drugs and metabolites – that are bound to plasma proteins
Eliminating undesirable substances - urea and uric acid - that were passively reabsorbed
Ridding the body of excess K+ - the aldosterone effect
Controlling pH by altering amounts of H+ or HCO3- in urine
What’s renal clearance?
o Renal Clearance: the volume of plasma that the kidneys can clear of a particular substance within a given time
o Renal clearance tests can determine GFR, detect glomerular damage, and follow the progress of renal disease
What are the treatment options for renal failure?
o Renal Failure: a GFR < 15 mL/min
Formation of filtrate dramatically decreases or completely stops
Uremia: “urine in the blood” – ionic and hormonal imbalances, metabolic abnormalities, toxic molecule accumulation
Symptoms: fatigue, anorexia, nausea, mental status changes, cramps
Treatment: hemodialysis or kidney transplant
Be prepared to answer a question about what is “normal” or “abnormal” to be found in urine. And review the chart to recall what abnormal findings may indicate.
o Chemical Composition
o 95% Water, 5% Solutes
o Nitrogenous Wastes
Urea: largest solute component; formed from breakdown of amino acids
Uric Acid: product of nucleic acid metabolism
Creatinine: metabolite of creatine phosphate – found in large amounts in skeletal muscle
o Normal Solutes in Urine: urea, Na+, K+, PO43-, SO42-, creatinine, uric acid
Ca2+, Mg2+, HCO3- are occasionally seen in small amounts
o Abnormal Solutes in Urine: blood proteins, WBCs, and bile pigments – presence of these can indicate pathology
Review the physical characteristics of urine (slide 25).
o Color and Transparency
Freshly voided urine is clear - pale to deep yellow
Urochrome: pigment that results from the body’s destruction of hemoglobin
More concentrated urine is deeper in color
Abnormal colors (pink, brown, red) can be caused by certain foods, medications, drugs, vitamins, and the presence of bile/blood
Cloudy urine may indicate a urinary tract infection (UTI)
o Odor
Only slightly aromatic when fresh
Upon standing, develops an ammonia odor as bacteria metabolizes urea
May be altered by some drugs, foods, and diseases
o pH
Slightly acidic (pH = ~6, range 4.5 to 8)
Acidic (high protein) or alkaline (vegetarian) diets will alter pH
Prolonged vomiting and UTIs can also raise pH
o Specific Gravity
Ratio of the mass of a substance to the mass of an equal volume of distilled water
Urine’s specific gravity ranges from 1.001 to 1.035
What’s the trigone of the bladder? What 3 openings form the trigone?
o Trigone: smooth triangular area outlined by the openings for the 2 ureters and the urethra
o Ureters: slender tubes that actively carry urine away from the kidneys towards the bladder
o Ureters are retroperitoneal continuations of the renal pelvis
o Enter the base of the bladder – through the posterior wall
o As bladder pressure increases, the distal ends of the ureters prevent backflow of urine into the ureters
o Three Layers:
Mucosa
Muscularis: smooth muscle that contracts in response to stretch
Adventitia
o Urethra: muscular tube that drains the urinary bladder
o Mucosal lining is largely pseudostratified columnar epithelium – transitional epithelium near the bladder – stratified squamous near the external opening
o Urethral Sphincters:
Internal Urethral Sphincter: involuntary/smooth muscle at the bladder-urethral junction – contracts to open
External Urethral Sphincter: voluntary/skeletal muscle surrounding the urethra as it passes the pelvic floor – relaxes to open
Name the smooth muscle of the bladder.
What is considered the “max capacity” of the bladder?
o When empty, the bladder collapses and rugae appear
o During filling, the bladder expands and rises superiorly, but there is no significant rise in internal pressure
o Moderately Full Bladder:
~12 cm/5 in long
500mL/1 pint of urine
o Max capacity is about 1,000mL – an overfilled bladder can burst!
Compare/contrast the male and female urethras.
o Female
3-4 cm/1.5 in long
Tightly bound to the anterior vaginal wall
External urethral orifice is anterior to the vaginal orifice
o Male
Carries both semen and urine
Much longer – 20 cm/8 in - has 3 named regions
* Prostatic Urethra: (2.5 cm) within prostate gland
* Intermediate/Membranous Urethra: (2 cm) passes through urogenital diaphragm from prostate to root of penis
* Spongy Urethra: (15 cm) passes through the penis, opens via external urethral orifice
Where are the internal and external urethral sphincters located?
o Internal Urethral Sphincter: involuntary/smooth muscle at the bladder-urethral junction – contracts to open
o External Urethral Sphincter: voluntary/skeletal muscle surrounding the urethra as it passes the pelvic floor – relaxes to open
Outline the micturition reflex – as is done on slide 33! What sphincter relaxes to open? Which contracts? Which sphincter is autonomically controlled? Which is somatically controlled?
o Three Simultaneous Events
Contraction of the detrusor muscle by ANS
Opening of internal urethral sphincter by ANS
* Opens via contraction!
Opening of external urethral sphincter by somatic nervous system
* Opens via relaxation!
