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PHGY 210 Study Set Exam
Kidney Functions - Answer 1. regulation of water, inorganic ion balance, acid-base balance
- removal of metabollic waste products from blood and excretion in urine
- removal of foreign chemicals from blood and excretion in urine (ex. antibiotics)
- production of hormones/enzymes
- erythropoietin: controls erythrocyte production
- renin: controls angiotensin formation and BP, Na balance
- 1,25-dihydroxyvitamin D: active vitamin that influences Ca balance kidney weight - Answer 150 g each kidney location - Answer behind peritoneum on either side of vertebral column against posterior abdominal wall kidney anatomy - Answer renal cortex, renal medulla, renal pelvis, renal artery, vein, ureter renal artery - Answer interlobar arteries (passes from pelvis to medulla; branches into cortex) arcuate arteries (perpendicular to interlobar) nephron - Answer - gets blood from interlobar artery
- ~1 million per kidney
- consists of renal corpuscle (glomerulus (capillary loops + Bowmans capsule) and tubule nephron passage - Answer from corpuscle in cortex --> proximal tubule --> loop of Henle (descending and ascending) --> distal tubule (touches on glomerulus) --> cortical collecting duct --> medullary collecting duct renal corpuscle - Answer - glomerulus punching into Bowman's capsule Bowmans capsule - Answer parietal layer, space, visceral layer (podocytes) podocytes - Answer cell processes and cell body in glomerular capillary wall glomerular capillary wall - Answer filtration barrier
- entangled capillary loops surrounded by Bowman's capsule
- filters blood to make urine filtrate flow - Answer endothelial cells --> GBM (Glomerular Basement Membrane) --> podocytes renal corpuscle - Answer glomerulus (cortex) Bowman's capsule (cortex) proximal tubule - Answer proximal convoluted tubule (PCT) - cortex proximal straight tubule (PST) - cortex/medulla Henle's loop - Answer descending thin limb - medulla ascending thin limb - medulla thick ascending limb - medulla/cortex distal convoluted tubule - Answer DCT - cortex collecting duct - Answer cortical collecting duct (CCD) - cortex medullary collecting duct (MCD) - medulla nephron vascular supply - Answer efferent arteriole --> peritubular capillaries --> venous system urine formation - Answer 1. glomerular filtration
- tubular secretion
- tubular reabsorption glomerular filtration - Answer filtration of plasma from glomerular capillaries into Bowman's space
- filtrate is cell-free and except for proteins, has substances as plasma in same concentrations tubular secretion/absorption - Answer - as filtrate passes through tubules, composition altered
- reabsorption: tubules --> peritubular capillaries
- secretion: peritubular capillaries --> tubules Amount Excreted - Answer Amt excreted = amt filtered + amt secreted - amt reabsorbed (secretion =/= excretion) 3 substance pathways - Answer - complete secretion (ex. PAH para-amino-hippurate to
reabsorption tubular lumen --> peritubular capillaries - Answer - basolateral membrane, tight junction b/w tubular epithelial cells on tubular lumen, luminal membrane, interstitial fluid
paracellular - Answer through tight junction
transcellular - Answer through tubular epithelial cell
urea reabsorption rate - Answer low (44%) compared to water, Na, glucose (~100%) b/c is a waste product
2 mechanisms or reabsorption - Answer diffusion and mediated transport
diffusion - Answer across tight junction (paracellular) connecting tubular epithelial cells
- e.g. urea in proximal tubule: urea freely filtered in glomerulus, in proximal tubule water reabsorption, urea concentration higher, urea diffuses into peritubular capillaries and interstitial fluid
mediated transport - Answer - transcellular
- requires plasma membrane transport proteins
- usually coupled to Na reabsorption
solute transport mechs - Answer - passive: spontaneous, down electrochemical gradient (no energy); diffusion, channels, uniport, coupled transport, solvent drag
- active: against an electrochemical gradient (needs energy)
Transport Maximum (Tm) - Answer - when transport proteins in membrane saturated, tubule cannot reabsorb any more --> limit is Tm
- ex. in diabetes mellitus, plasma conc. of glucose can be very high and filtered load
exceeds capacity of tubules to reabsorb glucose (Tm exceeded) --> glucose in urine (glucosuria)
Tubular secretion - Answer - moves substances from peritubular capillaries to tubular lumen
- mediated by diffusion and transcellular mediated transport
- H and K most secreted by tubules
- usually coupled to Na reabsorption
division of labor in tubules - Answer - GFR must be large --> filtered volumes and loads large
- proximal tubule: reabsorbs most water and solutes, except K
- Henle's loop: also reabsorbs large quantites of major ions (less water)
- DCT/CD: water and solutes relatively small; fine-tuning; determines final excretion amt. by adjusting reabsorption (MOST HOMEOSTATIC CONTROL HERE)
clearance - Answer - volume of plasma from which that substance is completely removed (cleared) by kidneys/unit time
clearance of S (Cs) - Answer = mass of S excreted per unit time/ plasma conc. of S (Ps)
- mass S excreted per unit time = urine conc. S (Us) * urine volume per unit time (V) Cs = UsV/Ps
inulin clearance - Answer - polysaccharide administered intravenously; freely filtered at glomerulus, but not reabsorbed, secreted, or metabolized by tubule
- Cin = volume plasma initially filtered (GFR)
- ex. conc. inulin in plasma = 4mg/l; urine V = 2.4 l/day; inulin conc. in urine = 300 mg/l; amt inulin excreted in urine = 2.4 l/day * 300 mg/l = 720 mg/day
- Cin = 720 mg/day / 4 mg/L = 180 L/day
- most accurate GFR marker
epithelial cells; each tubular segment has different mechs
- on promixal tubule: Na-H antiporter (counterporter)
- on CCD: diffusion via Na channel
renal sodium regulation - Answer increased Na intake --> increased Na excretion and vice versa
- Na excreted = Na filtered - Na reabsorbed (Na not secreted)
- regulated by GFR (minor role) and Na reabsorption (most important)
sensing total body sodium - Answer - Na major extracellular solute, changes in total body sodium --> changes in ECF volume
- total body Na sensed as intravascular filling by baroreceptors in cardiovascular system
- plasma conc. of Na not a marker for total body sodium b/c very different across different water compartments
- Pna only reflects relative relationship of total body Na and water
Na regulation by GFR - Answer increased Na conc./H2O loss --> decreased plasma and venous BP --> decreased arterial BP --> increased renal sympathetic nerve activity --> (in kidneys) afferent arteriole constriction --> decrease in GFR --> decrease in Na and H2O excretion
Na regulation by reabsorption - Answer (PT 67%, TAL 25%, CCD 3%, IMCD 1%)
- aldosterone (steroid hormone secreted by adrenal cortex, zona glomerulosa)
- aldosterone stimulates Na reabsorption in DCT and CCD
- no aldosterone: ~2% filtered load excreted (eq. to 35 g NaCl)
- high aldosterone: ~0% filtered load excreted
- aldosterone acts on Na/K diffusion across luminal membrane and K/Na ATPase pump to upregulate expression
regulation of aldosterone secretion - Answer renin-angiotensin system
- liver secretes angiotensinogen, kidneys secrete renin to blood
- in blood: renin causes angiotensinogen --> angiotensin I -(converting enzyme ACE)-> angiotensin II --> secretes aldosterone in adrenal cortex
- ANP: negative regulation
- ACTH and increase in plasma K: positive regulation
juxtaglomerular apparatus - Answer - juxtaglomerular cells on afferent arteriole secrete renin through macula densa cells of TAL
regulation of renin secretion by ECF volume - Answer - important for Na balance
- aldosterone doesn't stimulate H2O reabsorption directly in CCD
Atrial Natriuretic Peptide - Answer ANP
- peptide hormone secreted by cardiac atria cells
- acts on tubules to inhibit Na reabsorption (opposite aldosterone) and increases GFR
- increased total body Na (increased ECF/plasma) stimulates ANP secretion
BP regulation of Na - Answer increased BP increases Na excretion (pressure natriuresis)
ANP action - Answer - increased plasma V --> increased distention of cardiac atria --> increased ANP secretion --> increased plasma ANP --> decreased plasma aldosterone --> afferent arteriole dilation, efferent arteriole constriction --> increased GFR --> decreased Na reabsorption --> increased Na excretion
osmolarity - Answer total solute conc. of solution; measure water conc. in that the higher solution osmolarity, lower water conc.
hypoosmotic - Answer total solute conc. less than normal ECF (300 mOsm)
countercurrent multiplier system - Answer - medullary ISF becomes hyperosmotic through Henle's loop and countercurrent flow
- distal actively reabsorbs NaCl; impermeable to water
- proximal doesn't reabsorb NaCl; permeable to water
- at proximal end, water leaves lumen, causing higher osmolarity
- at distal end, due to high osmolarity, NaCl leaves the lumen, causing osmolarity to decrease below 300 mOsm
- Osm highest at bottom of loop (1400 mOsm)
- ISF between loop mirrors increase in Osm as go down
vasa recta - Answer blood vessels in medulla
- hairpin-loop structure, minimizes excessive solute loss from interstitium
- in addition to NaCl, also contributes to medullary hyperosmolarity
water permeability of tubules - Answer - water reabsorption depends on tubule permeability
- permeability of epithelium depends on tubular segment (e.g. proximal tubule high in water permeability)
- permeability largely depends on presence of water channels (aquaporins) in plasma membrane
- water permeability (regulated by aquaporin amts in plasma membrane) in CCD and MCD subject to phgy control - vasopressin is key hormone
vasopressin - Answer - peptide hormone, also called anti-diuretic hormone (ADH)
- produced by group of hypothalamic neurons
- released from posterior lobe of pituitary gland
- couples to GPCR V1 (smooth muscle) and V2 (kidney)
- vasopressin stimulates insertion of aquaporins in luminal membrane of collecting duct cells and increases water permeability, increases water reabsorption
- vasopressin not present: CDs impermeable to water --> water diuresis
- diabetes insipidous (DI) caused by malfunction of vasopressin system, vasopressin doesn't work
vasopressin regulation - Answer - water excretion mainly regulated by rate of water reabsorption from tubules; vasopressin regulates this rate
- osmoreceptor control (most important)
- baroreceptor control (less sensitive)
osmoreceptor control of vasopressin secretion - Answer excess water --> decreased body fluid osmolarity --> decreased firing of hypothalamic osmoreceptors --> decreased vasopressin secretion (posterior pituitary) --> decreased plasma vasopressin --> decreased tubular permeability to H2O --> decreased water reabsorption (in CD) --> increased water excretion
baroreceptor control of vasopressin - Answer decreased plasma --> decreased venous, arterial P --> increased vasopressin secretion --> increased plasma vasopressin --> increased tubular permeability to H2O --> increased water reabsorption --> decreased water excretion
severe sweating - Answer loss of water > loss of Na
thirst - Answer due to increased plasma osmolarity --> osmoreceptors
K abundance - Answer - most abundant intracellular ion
- 98% ICF, 2% ECF
- conc. important for excitable tissue function (nerve + muscle) b/s resting membrane potential directly related to relative intracellular and extracellular K concentrations
- deviations in conc. cause abnormal heart rhythms and skeletal muscle contraction (tachycardia)
- pH ~ 7.4 ([H]: ~40 nmol/L)
important mass reaction - Answer CO2 + H2O <--> H2CO3 (carbonic anhydrase) --> HCO3- + H+
- when bicarbonate ion lost from body, same as if body gained H
- when body gains bicarbonate, same as if body loses H
nonvolatile acids - Answer - phosphoric acid, sulfuric acid, lactic acid
gain H - Answer from CO2, nonvolatile acids, loss of bicarbonate in GI fluids, urine
lose H - Answer from metabolism of anions, vomitus, urine, hyperventilation
H buffer - Answer - any substance that can reversibly bind H is a buffer
- pH = -log[H]
- normal ECF pH 7.4 corresponds to 40 nM H
- w/out buffering, H conc. changes a lot
- major extracellular buffer is CO2/HCO3 system
- major intracellular buffers are phosphates and proteins
- buffering doesn't remove H from body, only keeps them locked up
ultimate H balance - Answer - controlled by respiratory sys (by controlling CO2) and kidneys (by controlling HCO3)
- both work to minimize change of [H]
renal mechs of H control - Answer - low H conc. (high pH: alkalosis) --> kidneys excrete HCO
- high H conc. (low pH: acidosis) --> kidneys produce new HCO3, add to plasma
renal handling of HCO3 - Answer - HCO3 excretion = HCO3 filtered +HCO3 secreted - HCO3 reabsorbed
- normally, kidneys reabsorb all filtered HCO3 (exception if alkalosis)
- also mediated by H/K-ATPase and Na/H antiporter
HCO3 reabsorption distribution - Answer 80% PT 15% TAL 5% CCD
addition of new HCO3 to plasma - Answer via
- H secretion and excretion on non-bicarbonate buffers (such as phosphate)
- glutamine metabolism w/ NH4+ excretion
- both processes viewed as H excretion by kidney
- kidneys normally contribute enough new HCO3 to plasma to compensate for H from nonvolatile acids generated in body (40-80 mmol/day)
- happens only after all HCO3 reabsorbed and no longer available in lumen
alkalosis - Answer low H conc. (high pH)
- respiratory alkalosis (from altered respiration)
- metabolic alkalosis (from other causes)
acidosis - Answer high H conc. (low pH)
- respiratory acidosis (from altered respiration)
- metabolic acidosis (from other causes)
renal response to acidosis - Answer 1. sufficient H secreted to reabsorb all filtered HCO
metabolic alkalosis - Answer decreased H, increased HCO3, increased CO
- HCO3 due to primary abnormality
- CO2 due to reflex ventilatory compensation
- ex. vomiting (loss of H); hyperaldosteronism (increased H secretion in DCT and CCD)
diuretics - Answer - drugs used to clinically increase volume of urine excreted
- act on tubules to inhibit Na reabsorption along w/ Cl and/or bicarbonate, resulting in increased ion excretion; water excretion also increases
loop diuretics - Answer - acts on thick ascending limb of Henle
- inhibits cotransport of Na, Cl, K (Na-K-2Cl cotransporter)
- commonly used
- e.g. furosemide
K-sparing diuretics - Answer - inhibit Na reabsorption in CCD, also inhibits K secretion there; thus unlike other diuretics, plasma conc. of K doesn't decrease
- either block aldosterone action or block (aldosterone-regulated) epithelial Na channel in CCD
- e.g. amiloride, spironolactone
clinical use of diuretics - Answer - renal retention of salt and water: abnormal expansion of ECF (edema)
- ex. 1 congestive heart failure (cardiac failure leading to less cardiac output) ex. 2 hypertension: in some patients w/ hypertension, renal retention of Na and water contribute to high BP
kidney disease/failure - Answer - proteinuria (protein is urine)
- accumulation of waste products in blood (urea, creatinine, phosphate, sulfate)
- high K conc. in blood
- metabolic acidosis
- anemia (decreased secretion of erythropoietin)
- decreased secretion of 1,25-(OH)2 vitamin D (leading to hypocalemia)
renal failure treatment - Answer - when >90% nephrons working, cannot sustain life, need renal replacement therapy
renal replacement therapy - Answer 1. hemodialysis
- peritoneal dialysis
- kidney transplantation
hemodialysis - Answer arterial blood from patient --> blood pump -(anticoagulent)->dialyzer (removes waste from blood) --> air trap and air detector --> venous blood to patient
peritoneal dialysis - Answer - lining of patients own abdominal cavity (peritoneum) used as dialysis membrane
- fluid injected into cavity via tube through abdominal wall
- solutes diffuse into fluid from person's blood
- fluid exchanged several times per day
kidney transplantation - Answer - either from recently deceased (cadaveric transplant) or living related/unrelated donor
- anti-rejection treatments have improved dramatically
- donors can function normally with one kidney
GIT homeostatic role - Answer provide nutrients to body
- external environment --> food --> GIT --> absorbable molecules --> internal environment
- secretion (glandular activity - endocrine and exocrine) - chemical breakdown
- absorption - transfer to blood circulation
GIT digestive/absorptive capacity - Answer - carb 99%
ENS - Answer enteric nervous system
- independent though may receive input
- initiates, programs, regulates, coordinates
GIT wall innervation - Answer - plexus - collections of nerve cell bodies
- submucosal plexus, myenteric plexus (in muscularis externa)
- contain elements for reflex arcs:
- sensory neurons w/ receptors in mucosa or muscle; stretch, chemo, etc...
- effector neurons that activate secretory and muscle cells
- many interneurons which expand responses to stimuli in GIT
- precise and graded activity due to circuitry
- although distinct, 2 plexuses behave as one unit
Ach (M) - Answer excitatory, blocked by atropine
NANC - Answer inhibitory, non-adrenergic, non-cholinergic
enteric neurons and transmitters - Answer Ach and NANC innervate smooth muscle cells
- ultimate activity = algebraic sum of innervations
short, enteric (intrmural) reflexes - Answer stimulus innervates chemoreceptors, osmoreceptors, mechanoreceptors in gut wall --> nerve plexus --> smooth muscle or gland cell --> response
ANS innervation of GIT enteric neurons - Answer - parasympathetic (preganglionic): nicotinic excitatory - CNS innervates ENS w/ ACh
- sympathetic (postganglionic): NA inhibitory - CNS innervated ganglion w/ ACh, which then innervated ENS with NA
- when innervate ENS, can either innervate an excitatory (ACh) or inhibitory (NANC) that innervates smooth muscle cell
vagus nerve - Answer from medulla in CNS, covers most of GI tract except pelvic nerves which control colon/rectum
ANS modulates ENS - Answer - allows for integrated activity over longer distances along GIT
- long, extrinsic reflexes
- in general: PS - excitatory (may also excite inhibitory neurons), S - inhibitory (may also inhibit inhibitory neurons)
hormonal regulation - Answer - non-GIT hormones may influence growth and development of GIT
- GIT hormones may influence activities outside the GIT
- GIT hormones regulate activities inside the GIT
ghrelin - Answer stimulates hunger in hypothalamic feeding center
- releasing from stomach during fasting
leptin - Answer induces satiety in hypothalamic feeding center
- released from adipose cells
