Intro to Renal Physio Flashcards
Kidney’s endocrine function
EPO (peritubular capillary cells), Vitamin D/Calcitriol (tubule cells, PTH and 1-alpha hydrogenase)
Kidney and CV systems are
interdependent
Functional unit of kidney
nephron
two parts of a nephron
Bowman’s capsule/gomerulus and tubule
Cortical nephron
glomeruli in cortex, Loop of Henle dips into outer medulla (electrolyte excretion)
Juxtamedullary nephron
glomeruli in cortex, Loop of Henle dips DEEP into inner medulla (urine concentration)
Path of blood from renal a to renal v
renal a -> afferent arteriole -> glomerular capillaries -> efferent arteriole -> pertitubular capillaries (cortical loops and medullary loops (vasa recta)) -> renal v
Bowman’s space
space between glomerular capillary and tubule, collects filtrate
JGA
thick ascending limb passes through angle of afferent and efferent arterioles
Macula Densa
specialized cells in the thick ascending limb
sense NaCl flow through tubule and send feedback to afferent arteriole’s juxtaglomerular cells
Tubuloglomerular Feedback
communication about NaCl flow from the macula densa to the glomerular arteriole
Renin producing cells are located _______
in the afferent arteriole adjacent to the macula densa
Extraglomerular mesangial cells
participate in transmitting infor from macula densa to afferent and efferent arterioles
What is the site of renin release
JGA
3 causes for renin release
renal SNS, decreased stretch or flow through afferent arteriole (renal baroreceptor), and stimulation from the macula densa ([NaCl])
Function of Renin
catalyzes Angiotensinogen –> Angiotensin I/II (ACE) which leads to the production of aldosterone by the adrenal cortex
Renin promotes the activation of what 2 hormones
Aldosterone (adrenal cortex) and ADH
Function of Aldosterone
(adrenal cortex) –> increases the activity of Na/K-ATPase -> increase Na+ followed by H2O reabsorption
Function of ADH
translocation of aquaporins to the surface of the collecting duct -> increase H2O reabsorption
SNS on renal function
Vasoconstriction of afferent and efferent arterioles
SNS impact on JGA
increases release of renin from afferent and efferent arteriole granular cells
SNS impact on tubules
reabsorption of Na
SNS’s NT and receptor
NE and alpha-adrenergic
Function of Mesangium
structural support of glomerular capillaries, secretion of prostaglandins (dilation of afferents), secretion of cytokines, and are phagocytic
What happens when immune complexes (infection or autoimmune) clog mesangium area?
Inflammatory response -> scarring -> loss of glomerular function -> renal failure
Proteinuria is a marker of
systemic endothelial cell dysfunction
Proteinuria may be a result of kidney damage but may also ___________
cause tubular and interstitial inflammation, ishemia, and fibrosis
Hypoalbuminemia via proteinuria
excessive loss of plasma protein, formation of peripheral edema, alters acid-base balance, and circulating hormones
4 types of proteinuria
Glomerular, tubular, exercise, and orthostatic
3 Layers to the glomerular filtration barrier
endothelium w/ fenestra, basement membrane, podocytes
Endothelium of the glomerular filtration barrier
large fenstra with negatively charged glycoproteins (not a size barrier - 70um)
Basement Membrane of the glomerular filtration barrier
composed of ECM, negatively charged
Podocytes of the glomerular filtration barrier
Negatively-charged podocytes create filtration slits which is covered by a slit diaphragm
Slit Diaphragm of the glomerular filtration barrier
thin, negatively-charged, selectively porous membrane
What protein largely makes up the slit diaphragm and
nephrin
What passes through the slit diaphragm?
H2O and electrolytes (unless damage has occurred)
glomerular filtration barrier size barrier
20-42A; easily passes molecules 42A
glomerular filtration barrier between the range of 20-42A
Dependent on charge and size, a cationic molecule will pass more easily
Albumin does not pass the glomerular filtration barrier because
IT is highly NEGATIVELY-charged, size is irrelevant because it is 36A
Size of albumin
36A
Glomerular proteinuria may be due to
physiologic or pathological, transient or permanent, and can cause huge loss of protein
Would it be more worrisome to have positive or negative proteins in the urine?
Negative; because the negatively charged glomerular filtration barrier should prevent the passage of negative molecules
Loss of glomerular charge selectivity is > or < important than loss of size selectivity on Albuminuria
Charge is more important because size is already within range of 20-42A
How would one detect the loss of glomerular size selectivity
you would see medium-sized proteins (like albumin) and larger proteins (like IgGs) in the urine
What level of proteins are normally found in urine?
<20), plasma proteins, and renal tubule of urogenital tract proteins
What is microalbunimuria?
excretion of 30-300mg of albumin/day; indicative of vascular dysfunction
What is non-nephrotic proteinuria?
<3000mg/day excreted protein
What is nephrotic range proteinuria?
> 3000mg/day excreted protein; may include excessive sloughed off tubular cells, RBCs, lipiduria, peripheral edema if hypoalbuminemia
If protein is filtered where would it be reabsorbed? (<20A or plasma protein)
proximal tubule via endocytosis
What protein can be measured to determine if the proximal tubule is functioning properly?
Beta-2 microglobulin; this protein is small and freely filtered but generally reabsorbed via endocytosis
Proximal tubular damage may be caused by
ischemia, immunological damage, or heavy metal intoxication damage
What will happen with albumin during proximal tubular damage?
albumin in urine will increase slightly bc it is still restricted by the glomerulus, but the small amount that enters the filtrate will not be reabsorbed
Dip stick lab tests may identify which types of proteinuria
Glomerular proteinuria (large amounts of albumin) BUT NOT tubular proteinuria bc there is still a SMALL amount of albumin that is excreted
What is overflow tubular proteinuria?
Small proteins that are filtered as filtrate normally are reabsorbed, but if they are filtered in excessive amounts the amount may exceed the body’s ability to reabsorb them (NOT due to tubular damage)
2 types of non-pathological proteinuria
Exercise and orthostatic
Exercise proteinuria
strenuous exercise leads to transient increase in protein excretion (albumin); can be tubular and glomerular proteinuria
Orthostatic proteinuria
Upright position increases the excretion of protein (normal when lying down)
Control of Micturition
internal and external urethral sphincter
Internal urethral sphincter
involuntary, smooth muscle, tonic contractile tone (until pressure threshold of filling is reached)
external urethral sphincter
skeletal muscle, voluntary, innervated by the pudendal n
Pudendal n
innervates external urethral sphincter and carries sensory afferents from bladder and urethra
Detrusor muscle
smooth muscle that surrounds the epithelial lining of the bladder
Sacral n (pelvic n) carries
parasympathetic efferents to the detrusor muscle for voiding bladder (M3 receptor); sensory afferents (info to spine on fullness of bladder)
Hypogastric n.
Sensory afferents (info to spine on fullness of bladder), efferents to bladder neck for contraction and storage of urine (alpha receptors) and some efferents to detrusor for relaxation (Beta-3 receptor)
3 nerves that supply the bladder and their function
Pudendal n (S2-S4): somatic innervation of external urethral sphincter Hypogastric n (L1-L3): sympathetic innervation to the bladder neck for contraction and filling and to detrusor for relaxation; sensory afferents Sacral (Pelvic) n (S2-S4): parasympathetic innervation to detrusor muscle for voiding; sensory afferents
Micturition Reflex
spinal reflex that is modified by higher brain centers (pontine micturition center)
What happens if the higher brain centers are separated from the spinal control of micturition?
Incontinence
First step in micturition reflex
Bladder filling causes stretching of the detrusor muscle causing afferent sensory information to be sent to the spinal cord (150mL mild “fullness” signal and 400mL very strong signal)
Second step in micturition reflex
parasympathetic efferent signal sent back to detrusor muscle causing contraction (may cause internal urethral sphincter to open)
Once urine begins entering urethra and a second set of sensory afferents, ________
sympathetic signal is sent to the bladder neck and internal urethral sphincter that inhibits its tonic contraction
The final step in micturition is
voluntary relaxation of the external urethral sphincter allows voiding
Higher brain function can modify the afferent signals and micturition reflex
inhibit the parasympathetic contraction of the detrusor muscle, to avoid voiding. (decreased the sensitivity to the micturition reflex)
What would happen to the micturition reflex if the spinal cord was transectioned?
Voluntary control is obliterated, and the micturition reflex will simultaneously contract the detrusor and EUS interfering with voiding
What would happen to the micturition reflex if sympathetic nerves were blocked?
Nothing
Urge Urinary Incontinence
involuntary leakage accompanied by the feeling of urgency; overactive parasympathetics to detrusor (treated by anti-cholinergic) or interstitial cystitis “painful bladder syndrome”
Stress Urinary Incontinence
involuntary leakage accompanied by increased intra-abdominal pressure (coughing, sneezing); due to insufficient urethral sphincter
Overflow Urinary Incontinence
Inability to completely empty bladder -> large bladder volume -> dribbling -> due to obstruction (BPH in men)or underactive parasympathetic innervation to the detrusor muscle
Urinary Incontinence due to transient conditions
not associated with a lower UT dysfunction; bladder infection, increased urine production, mental status, medications
