Intro To Renal Physiology Flashcards

1
Q

Functions of kidney as endocrine organ

A

. Production of EPO from peritubular fibroblast-like cells in cortical interstitium
. Regulation of calcitriol (1,25-dehydroxy vit. D3) in prox. Tubule cells via activity of 1alpha-hydrooxylase

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2
Q

EPO function

A

. Regulates process of differentiation of uncommitted stem cells toward erythrocyte lineage

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3
Q

1alpha-hydroxylase

A

. Under control of PTH and plasma phosphate

. Net effect is to inc. plasma Ca and P

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4
Q

Calcitriol function

A

. Regulates gut Ca and P absorption

. Secondary effects in bone in kidney

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5
Q

How kidney and CV systems are interdependent

A

. Kidney affects ECF volume which affects CO

. Kidney is controlled by CO and peripheral resistance

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6
Q

Nephron

A

. Functional unit of kidney
. Each kidney has 1.2 million
. Composed of glomerulus/Bowman’s capsule and the tubule

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7
Q

Structure of tubule

A

. Prox tubule
. Loop of Henle (descending and ascending limbs)
. Distal tubule
. Collection duct system

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8
Q

Cortical and juxtamedullary nephrons

A

. All glomeruli lie in cortex
. Cortical nephrons: loop of Henle dip is into outer medulla
. Juxtamedullary nephron: loop of Henle dips deep into the inner medulla

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9
Q

Segments of tubule

A
. Prox convoluted tubule (PCT)
. Prox straight tubule (PST)
. Thin descending limb (TL)
. Thick ascending limb (TAL)
. Distal convoluted tubule (DCT) 
. Connecting tubule (CNT) 
. Collecting duct (cortical, outer medullary, and inner medullary portions)
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10
Q

Renal circulation

A

. Renal a. -> afferent arteriole ->glomerular capillaries -> efferent arteriole -> peritubular capillaries (cortical and medullary loops/vasa recta) -> renal vein

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11
Q

Glomerulus

A

. Tuft of capillaries supplied by afferent arteriole and drained by efferent arteriole
. Glomerulus is ticked into closed end of nephron (Bowman’s capsule)
. Space btw capillaries and the start of the tubule (Bowman’s space)
. Collects filtrate from capillaries

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12
Q

Juxtaglomerular apparatus

A

. Where TAL passes through angle formed by afferent and efferent arterioles of nephron
. Components: macula densa, renin producing cells (JG cells) of afferent arteriole, extraglomerular mesangial cells
. Site of renin release

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13
Q

Macula densa

A

. Specialized cells in TAL
. Respond to changes in tubular flow of NaCl
. Sends signals to afferent arteriole that affect blood flow and filtration
. Communicate to glomerular arteriole i tubuloglomerular feedback

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14
Q

Extraglomerular mesangial cells

A

. Participate in transmitting info from macula densa to afferent and efferent arterioles

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15
Q

Control of renin release

A

. Renal sympathetic nn.: inc. signaling inc. renin
. Pressure in renal afferent aa.: mechanical (renal baroreceptor), Lou pressure inc. renin, high pressure dec. it
. Signals from macula densa:

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16
Q

SNS innervation locations in renal system

A

. Arteries, afferent and efferent arterioles: vasoconstriction from smooth mm. Constriction
. Juxtaglomerular apparatus: stimulates release of renin from granular cells of afferent and efferent arterioles
. Renal tubules: enhances Na reabsorption via alpha-adrenergic receptors

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17
Q

Mesangium

A

. Mesangial cells and mesangial ECM
. Mesangial cells surround capillaries, provide structural support, secrete prostaglandins and cytokines and are phagocytic
. Deposition of immune complexes triggers mesangial cell inflammatory response tha can lead to glomerular scarring and loss of glomerular function (eventually lead to renal failure)

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18
Q

Proteinuria

A

. Protein in urine
. Can be marker of systemic endothelial dysfunction
. Promotes tubular and interstitial inflammation, ischemia, fibrosis
. Early sign of renal dysfunction
.excessive loss of plasma protein in urine can cause hypoalbuminemia promoting peripheral edema that alters acid/base balance and circulating levels of hormones

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19
Q

Types of proteinuria

A

. Glomerular
. Tubular
. Exercise
. Orthostatic

20
Q

Ultrastructure of glomerulus

A

. Filtration barrier has endothelium, basement membrane, and podocyte foot processes/slit diaphragm

21
Q

Glomerular endothelium

A

. Fenestrated
. Surface has neg. charged glycoproteins
. Not much of size barrier to plasma proteins

22
Q

Glomerular Basement membrane

A

. Composed of extracellular protein matrix

. Negatively charged

23
Q

Podocytes and slit diaphragm

A

. Cell negatively foot processes
. Interdigitate to cover basement membrane
. Gaps btw foot processes (filtration slits) are covered by thin, selectively porous, neg. charged membrane (slit diaphragm)
. Pores in slit diaphragm pass water and electrolytes but selectively restrain larger plasma proteins

24
Q

Size and charge selectively of the glomerular capillary wall

A

. Easily passes molecules under 20A in radius (H2O, electrolytes, glucose, urea)
. Restricts anything over 42A
. Ease of passage btw 20-42 depends on molecular size and charge
. Cationic protein filtered easier than an ionic protein

25
Q

Glomerular proteinuria

A

. Appearance of large neg. charged proteins in urine
. Physiologic or pathologic
. Transient or permanent
. Can result in loss of massive quantities of protein if barrier is severely compromised
. Includes medium sizes proteins but can have larger sized proteins is size selectivity is what is affected
.

26
Q

Albumin

A

. Major plasma protein
. Marker of glomerular capillary wall integrity
. Radius of 36A and is neg. charged
. Loss of glomerular selectivity inc. filtration omg it
. Loss of glomerular size selectivity also inc. filtration

27
Q

ACR

A

. Urine albumin: creatinine ratio
. Ratio under 3 is desirable
. Creatinine is freely filtered normally

28
Q

Microalbuminuria

A

. Excretion btw 30 and 300 mg/24 hr
. ACR over 2.5 mg/mmol in me or over 3.5 mg/mmol in women
. Indicates vascular dysfunction
. Risk factor for inc. cardiovascular morbidity esp, in patients w/ DM and hypertension
. Physicians screen high risk patients

29
Q

Non-nephrotic proteinuria

A

. Total protein excretion over 0.5 g/day but less than 3g/day
. ACR over 30 mg/mmol clinically significant in adults w/o DM
. Would be detects w/ typical protein dipstick screening

30
Q

Nephrotic range proteinuria

A

. Large amount of daily total protein loss (over 3g/day)
. ACR over 220 mg/mmol
. Assoc. w/ other abnormal findings on urinalysis (excessive amt of cast-off tubular cells,RBCs and lipiduria)
. Patients can also have peripheral edema if hypoalbuminemia is present

31
Q

Tubular proteinuria

A

. Much of filtered protein (small proteins under 20A and larger proteins) is reabsorbed in prox. Tubule by endocytosis
. Small, freely filtered plasma protein typically measured in urine is beta=2 microglobulin
. Occurs when endocytosis process is impaired from hypoxia, immune damage, or heavy metal intoxication) and person excretes large amts of small proteins
. Is not detected by protein dipsticks

32
Q

Overflow tubular proteinuria

A

. Excessive excretion of low molecular weight proteins occurs Due to filtered load of protein exceeding ability of prox. Tubule to reabsorbed it
. Can occur from excessive production of immunoglobulin light chains in multiple myeloma, rhabdomyolysis and red cell lysis
. Can be due to excessive exposure to myoglobin, Hb, or immunoglobulin light chains

33
Q

Exercise proteinuria

A

. Strenuous exercise leads to transient inc. in protein excretion
. Resolves w/in a few hrs
. Can be both tubular and glomerular depending on intensity/duration of exercise

34
Q

Orthostatic proteinuria

A

. Assumption of an upright position inc. protein excretion

. Nighttime or recumbent protein excretion normal

35
Q

Bladder components

A

. Body (fundus) that stores urine
. Bladder neck that connects to urethra
. Epithelial lining: surround by smooth mm. (Detrusor) that is electrically coupled under ANS control
. Internal sphincter: thickening of bladder all at bladder neck (tonic contractile tone, is not voluntary)

36
Q

External urethral sphincter

A

. Skeletal muscle innervated by alpha-motor neurons carried in pudendal n.
. Voluntary control of this sphincter can be learned (after 2)
. Pudendal n. Also carries sensory afferents from bladder neck and urethra

37
Q

Sacral nn. Components

A

. Sensory afferents: nn. Send info to spinal cord on fullness of bladder
. Parasympathetic efferent: nn. Cause detrusor m. To contract (empties bladder), mostly via M3 receptors, active during voiding, inhibited during filling

38
Q

Sympathetic innervation of bladder

A

. Sensory afferents: sensory info on fullness and sensory input from bladder neck and urethra
. Efferent: cause contraction via alpha receptors in bladder neck, some innervation via B3 receptors tat mediate relaxation
. Active during filling of the bladder, inhibited during voiding
. Don/t appear to be important in filling process

39
Q

Micturition reflex

A

. Spinal reflex that is substantially modified by higher brain centers (brainstem, hypothalamus, and cortical areas)

40
Q

Steps in micturition reflex

A

. As bladder fills the smooth mm. Stretches, bp inc. and sacral sensory afferents stimulates
. When volume hits 150 ml mild signals, 400 ml strong feeling
. Parasympathetic efferents activated in response to sensory info and detrusor contracts, internal sphincter opens, and urine goes to urethra
. Stretching of urethra sends a signal to spinal cord to inhibit topically-active alpha motor neurons innervating external sphincter
. Relaxation of external sphincter occurs and voiding results

41
Q

Higher brain center regulation of micturition reflex

A

. Regulates sensitivity of reflex
. Sensitivity inc. when emptying of bladder is desired (voluntary voiding)
. Sensitivity of reflex reduced when emptying of bladder is not wanted
. Loss of cortical control will eliminate voluntary control of voiding, but often has simultaneous signals to contract detrusor and external sphincter that interfere w/ effective bladder emptying
. Loss of sympathetic nn. Doesn’t have much of an effect on bladder filling or voiding
. Can occur w/ paraplegia

42
Q

Urge incontinence

A

. Sudden need to empty the bladder that is difficult to delay
. Involuntary leakage accompanied by the feeling of urgency
. Condition of detrusor overactivity can lead to urge incontinence
. Interstitial cystitis/painful bladder syndrome assoc. w/ urgency and frequent bladder voiding
. Muscarinic blockade (anticholinergic meds) can be 1 pharmacologic strategy for detrusor overactivity

43
Q

Stress incontinence

A

. Involuntary leakage of urine assoc. w/ actions that inc. intra-abdominal pressure
. Pressure overwhelms that ability of sphincter to stay closed
. Severity dictates how much pressure change needs to occur to cause leakage
. Stress and urge incontinence often occur together in middle-aged and older women

44
Q

Overflow incontinence

A

. Inability to completely empty bladder leading to overflow
. Large bladder volume leading to continuous small amts of leakage
. Assoc. w/ bladder outlet obstruction (BPH)
. Can be poor detrusor contractility/underactivity from damage to parasympathetic afferents or efferents, aging, or trauma
. Nocturia, weak urinary stream, hard to start stream, intermittent streams
. Can be side effect of anti muscarinic therapy

45
Q

Incontinence due to transient or reversible conditions

A

. Not assoc. w/ primary dysfunction of lower urinary tract
. Not easily traced
. UTI, excessive inc. in urine production from uncontrolled DM or excessive fluid intake, mobility status of patients, meds, and cognitive function