Renal Physiology Exam

the urinary system

• functions of the urinary system

• Anatomy of the kidney

• Urine formation

  • glomerular filtration

  • Tubular reabsorption

  • Water conservation

• Urine and renal functions tests

• Urine storage and elimination

kidney functions

• filter blood plasma, eliminate (nitrogenous), waste, return useful chemicals to blood

• Regulate blood volume and pressure

• Regulate osmolarity of body fluids and electrolyte balance

• Secret erythropoietin → controls RBC count

• Help to regulate Pco2 and acid base balance

• Detoxify free radicals and drugs

• Gluconeogenesis (glucose from amino acids - only if starving

• Synthesize vitamin D3 → calcium balance

Nitrogenous wastes

1. Urea

   • proteins → amino acids → NH2 removed → forms ammonia (highly toxic), liver converts to urea

2. Uric acid

   • nucleic acid catabolism

3. Creatinine

   • creatinine phosphate catabolism (muscle)

renal failure

• azotemia: nitrogenous wastes in blood

• Uremia: syndrome due to toxic effects as wastes accumulate over a prolonged period of time

Path of blood through kidney

• renal artery →

  • interlobar arteries (up renal columns, between lobes)

  • Arcuate arteries (over pyramids)

  • Interlobular arteries (up into cortex)

  • Afferent arterioles

  • Glumerulus (cluster of capillaries)

  • Efferent arterioles (near medulla → vasa recta)

  • Interlobular veins → arcuate veins → interlobar veins

• Renal vein

  • 21% of cardiac output received by kidneys! (Remember kidney functions = blood homeostasis)

the nephron

• the kidney’s “functional unit” where blood is filtered and urine produced

• Two principal parts

  1. Renal corpuscle (blood filtration)

  2. Renal tubule (processes blood filtrate into urine)

• 1.2 million nephrons in each kidneys; each can be diagrammed as follows

renal tubule

• four major regions

  1. Proximal convoluted tubule (PCT)

     • longest most coiled simple cuboidal with brush border

  2. Nephron loop

     • U shaped descending + ascending limbs (AKA “loop of henle”)

     • Thick segment (simple cuboidal) initial part of descending limb and part or all ascending limb, active transport of salts

     • Thin segment (simple squamous) very water permeable

  3. Distal convoluted tubule (DCT)

     • cuboidal minimal micro ills

  4. Collecting duct

     • several DCT’s join

flow of glomerular filtrate

glomerular capsule → PCT → nephron loop → DCT → collecting duct → papillary duct → minor calyx → major calyx → renal pelvis → ureter. → urinary bladder → urethra

urine formation preview

1. Glomerular filtration creates a plasma like filtration of the blood

2. Tubular reabsorption removes useful solutes from the filtrate returns them to the blood

3. Tubular secretion removes additional wastes from the blood adds them to the filtrate

4. Water conservation removes water from the urine and returns it to blood concentrates wastes

filtration membrane

• fenestrated endothelium

  • 70-90nm pores exclude blood cells

• Basement membrane

  • proteoglycan gel, negative charge, excludes molecules >8nm

  • Blood plasma 7% protein → glomerular filtrate 0.03% proteins

• Filtration slits

  • podcyte arma have pedicels with negatively charged filtration slits allow particles <30nm to pass

filtration membrane

• almost any molecule smaller than 3nm can pass freely through the filtration membrane into the capsular space regardless of its charge (water electrolytes glucose fatty acids, amino acids, nitogenous waters, and vitamins)

• Some small molecules are retained in the blood because of their negative charge (e.g. albumin) or because they are bound to large plasma proteins that cannot pass through the membrane (calcium, iron, thyroid hormones)

• Various diseases and trauma can damage the filtration membrane and allow protein (albumin) or blood cells to enter the urine = proteinuria (albuminuria) or hematuria this can also occur temporarily after prolonged strenuous exercise (distance runner/swimmers)

filtration pressure

• the high “blood hydrostatic pressure” that drives the filtration process results from the fact that the afferent arterioles is so much larger than the efferent arterioles (glomerulus has large inlet and small outlet)

• Unlike most of the body’s capillaries the glomerular capillaries reabsorb little or no fluid they are engaged solely in filtration

• This high glomerular BP, makes the kidney especially vulnerable to hypertension → rupture of glomerular capillaries → scarring of the kidneys (nephrosclerosis) and thickening of the renal arteries (atherosclerosis) → reduces renal blood supply → renal failure

renal clearance

volume of blood plasma from which a particular waste is completely removed in 1 minute ( a measurement of “rate” or speed)

Renal function tests

• determine renal clearance (C) by assessing blood and urine samples: C = UV/P

  • U (waste concentration in urine (mg/mL))

  • V (rate of urine output (mL/min))

  • P (waste concentration in plasma (mg/mL))

• E.g. normally for urea: U = 6, V = 2, P= 0.2, so

  • C = 6 × 2 / 0.2 = 60 mL/min

  • If normal GFR is 125 mL/min then kidneys have only cleared 60/125 or 48% of filtrate (remember some urea is reabsorbed and this is normal/necessary)

Glomerular filtration rate (GFR)

• = amount of filtrate formed per minute by both kidneys

• In order to easily determine GFR in a patient we need to measure a substance whose concentration in the urine is unchanged after it has been filtered through the glomeruli (i.e. that is neither reabsorbed into the blood not secreted into the tubule after filtration has occurred)

• Insulin is polysaccharide produces by certain plants that neither reabsorbed nor secreted so for this solute

  • GFR = renal clearance = UV/P (normal = 125 mL/min)

• Insulin may be injected into the bloodstream and then measure in the urine → will indicate GFR exactly

• GFR can also be estimated from renal clearance of creatine which is not reabsorbed (but small amount of secretion so its renal clearance actually exceeds the GFR)

urine storage and elimination: Ureters

• about 25 cm long

• From renal pelvis passes dorsal to bladder and enters it from below

• As pressure builds ureters compressed → prevents urine from being forced out of the bladder into kidneys

• 3 layers

  • adventitia - CT binds to surrounding tissues

  • Muscularies - 2 layers of smooth muscle (urine enters → stretches and contracts in peristaltic wave

  • Mucosa - transitional epithelium

• Lumen very narrow, easily obstructed (stone - ouch)

urinary bladder

• located in pelvic cavity, posterior to pubic symphysis

• 3 layers

  • parietal peritoneum, superiority fibrous adventitia rest

  • Muscular is: detrusor muscle, 3 layers of smooth muscle

  • Mucosa: transitional epithelium

  • Trigone: opening of ureters and urethra, triangular arrangement → frequent site of UTI’s

  • Rugae: relaxed bladder wrinkled, highly distensible

  • Capacity: moderately full - 500 ml, max 7-800 ml

female urethra

• 3 to 4 cm long

• External urethral orifice

  • between vaginal orifice and clitoris

• Internal urethral sphincter

  • detrusor muscle thickened smooth muscle, involuntary control (predominates in infants)

• External urethral sphincter

  • skeletal muscle, voluntary control (predominates in adults)

Male bladder and urethra

• 18 cm long

• Internal urethral sphincter

• External urethral sphincter

• 3 regions

  • prostatic urethra

    • during orgasm receives semen

  • Membranous urethra

    • passes through pelvic cavity

  • Penile urethra

voiding urine - micturition

• micturition reflex

  1. 200 ml urine in bladder, stretch receptors send signals to spinal cord (S2, S3)

  2. Parasympathetic reflex arc from spinal cord , stimulates contraction of detrusor muscle thickened smooth

  3. Relaxation of internal urethral sphincter

  4. This reflex predominates in infants

  5. Micturition center in pons receives stretch signals and integrates cortical input (voluntary control)

  6. Sends signals for stimulation of detrusor and relaxes internal urethral sphincter

  7. To delay urination impulses sent though pudendal nerve to external urethral sphincter keep it contracted until you wish to urinate

  8. Valsalva maneuver

     • aids in expulsion of urine increase pressure on bladder

     • Can also activate micturition reflex voluntarily

glomerular filtration rate (GFR) is the amount of filtrate (mL) formed per minute

• filtration coefficient (Kf) depends on permeability and surface area of filtration barrier (averages 10-20% lower in women)

• For every 1 mmHg of “net filtration pressure” in men the kidneys produce 12.5 mL of filtrate/min

• GFR = NFP x Kf = 10 × 12.5 ~ 125 mL/min or 180 L/day (men) and 105 mL/min or 150 L/day (women) of filtration enters into the PCT

• On average 99% of filtrate reabsorbed and only 1 to 2 L urine excreted

effects of GFR abnormalities

• increase GFR urine output rises → dehydration electrolyte depletion

• Decrease GFR → wastes reabsorbed (azotemia possible)

• GFR controlled by adjusting glomerular blood pressure via 3 homeostatic mechanisms

  1. Autoregulation

  2. Sympathetic control

  3. Hormonal mechanisms: renin and angiotensin

autoregulation

• = ability of nephrons to adjust their own blood flow and GFR without external (nervous or hormonal) control and maintain relatively stable GFR despite changes in arterial BP

• Without it and increase in systemic BP of 25 mmHg would result in increased urine output of >40 L per day (i.e. helps to maintain stable fluid and electrolyte balance)

Two mechanisms of autoregulation

1. Myo genie

2. Tubuloglomerular

Myogenic mechanism

• smooth muscle tends to contact when stretched and relax when pressure reduces

• Afferent arteriole constricts when arterial BP rises to prevent blood flow into glomerulus from rising significantly and relaxes when arterial BP drops

tubuloglomerular feedback mechanism

• justaglomerular apparatus (JGA) monitors the fluid entering the distal convoluted tubule and adjusts GFR to maintain homeostasis

• JGA = JG cells + macula dense + mesanglial cells

tubuloglomerular feedback mechanism → juxtaglomerular apparatus

• increase BP → constricts afferent arteriole dilates efferent

• Decrease BP → dilates afferent arteriole constricts efferent

• GFR fluctuates within narrow limits for mean BP range of 80 to 170 mmHg

• Cannot compensate for extremes BP (e.g. mean BP below 70 mmHg, GF and urine output cease → “hypovolemic shock”)

sympathetic control of GFR

• strenuous exercise or acute condition (circulatory shock) stimulate afferent arterioles to constrict

• Lower GFR and urine production, redirecting blood flow to heart, brain and skeletal muscles where it is more urgently needed

hormonal control of GFR

if BP drops too far sympathetic NS also stimulates JGA to secrete enzyme called renin → converts a plasma protein called angiotensiogen to angiotensin → in lungs and kidneys angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II

Angiotensin II has the following BP-raising effects

• constricts efferent and afferent arterioles (reduces GFR and water loss)

• Stimulates secretion of antidiuretic hormone (ADH) Which promotes water reabsorption

• Stimulates adrenal cortex to secrete aldosterone (promotes sodium and water retention)

• Stimulates widespread vasoconstriction

• Stimulates thirst and thus encourages water intake

proximal convoluted tubules (PCT)

• here 65% of GF is reabsorbed into peritibular capillaries some substances also removed from blood for disposal in the urine (secretion)

• Great length prominent microvilli and abundant large mitochondria for active transport (6% of resting ATP and calorie consumption)

• Reabsorbed greater variety of chemicals than any other part of nephron two routes

  • tranacellular route - through epithelial cells of PCT

  • Paracellular route - between epithelial cells of PCT (“Leaky” tight junctions → water minerals, urea, etc)

• Reabsorbed substances enter ECF at base of epithelium → peritubular capillaries

reabsorption in the PCT

• sodium = “key” because it creates an osmotic and electrical gradient that drives the reabsorption of water and other solutes

• Reabsorbed into PCT epithelial cells by transcellular and paracellular routes

  • facilitated diffusion

  • Symport with glucose amino acids phosphate or lactate antiport with H+; etc.

• Pumped out of epithelial cells into ECF by Na/K pumps in basal and lateral plasma membrane

  • maintains much higher Na+ concentration in tubular fluid than tubule epithelial cells, despite Na+ uptake

chloride bicarbonate, potassium, magnesium and phosphate ion are all reabsorbed via various mechanisms

• sulfates and nitrates and not reabsorbed → urine

• Glucose is normally 100% reabsorbed by special “sodium-glucose transporters” → can become saturated (reach “transport maximum”) → “glycosuria” is a sign of DM

• Urea is 40-60% reabsorbed (but since water is 99% reabsorbed urine has much higher concentration of urea than blood) creatinine is not reabsorbed

• Water is 67% reabsorbed by PCT through paracellualr and transcellular osmosis (epithelial cells and surrounding tissue become hypertonic to tubular fluid → osmosis

Uptake by peritubular capillaries

mechanisms of capillary absorption

1. Osmosis

2. Solvent drag

Osmosis

• favoured by

  • high intestitial fluid pressure due to accumulation of fluid around base lateral sides of epithelial cells

  • Low blood hydrostatic pressure in peritubular capillaries (PCT) due to narrowed efferent arteriole

  • High colloid osmotic pressure in PTC due to fact that water filters through glomerulus by most blood proteins do not

solvent drag

Dissolved solutes are “pulled” into the PTC by the water as it moves into the PTC

Tubular secretion of PCT and nephron loop serves 2 purposes

1. Waste removal

   • urea, uric acid, bile salts, ammonia, catecholamines, many drugs and pollutants (‘toxins’)

2. Acid base balance

   • secretion of hydrogen and bicarbonate ions regulates pH of body fluids

the nephron loop

• primary function: generate a “salinity gradient” that enables the collecting duct to concentrate the urine and conserve water

• Also reabsorption of 25% of Na+, K+, and Cl- and 15% of the water of the glomerular filtrate

• Thick segment impermeable to water, but the above electrolytes reabsorbed → tubular fluid relatively dilute by the time it passes from the nephron loop into the DCT (i.e. high amount of water, low concentration of solutes)

DCT and collecting duct

filtrate reaching DCT has about 20% of water and only 7% of the salts that originally filtered through the glomerulus → 36 L/day (just be concentrated)

DCT and CD are subject to hormonal control

1. Aldosterone

2. Antidiuretic hormone (ADH)

3. Parathyroid hormone (PTH)

DCT and CD have 2 types of cells

1. Principle cells

   • more abundant, hormone receptors, water and salt balance

2. Intercalated cells

   • fewer, numerous mitochondria, acid base balance

Aldosterone (the salt retaining hormone)

• secreted by adrenal cortex in direct response to drop in blood Na+ or rise in K+ (or indirectly by drop in BP via angiotensin II mechanism)

• Causes DCT and cortical portion of CD to reabsorb more Na+ (followed by water and Cl- and secrete more K+

• Helps to increase/maintain blood volume and pressure

atrial natriuretic factor or peptide (ANF or P)

• secreted by atrial myocardium in response to high BP

• Results in excretion of more salt and water in the urine (thus reducing blood volume and pressure

parathyroid hormone (PTH)

• secreted by parathyroid gland in response to low plasma Ca++

• Promotes calcium reabsorption by ascending limb or nephron loop and DCT; inhibits phosphate reabsorption by PCT (decreases calcium and increases phosphate excretion)

• This prevents phosphate from binding with plasma Ca++ and forming new bone

• Increases / maintains plasma Ca++ levels

control of water loss by Collecting ducts

1. Producing hypertonic (concentrated) urine when poorly hydrates

2. Producing hypotonic (dilute) urine when well hydrated

producing hypertonic (concentration) urine when poorly hydrated

High blood osmolarity (concentration) stimulates release of ADH → stimulates renal tubule epithelial cells to synthesize aquaporins (water channel proteins) and install then in plasma membrane of CD → more water can pass through → CD reabsorbs more water which enters circulation though peritubular capillaries → urine output reduced and urine concentrated

Producing hypotonic (dilute) urine when well hydrated

ADH secretion decreases → tubule cells remove aquaporins → less water reabsorbed → urine dilute

collecting duct concentrates urine

• osmolarity of ECF is 4x higher deep in medulla than in cortex = “salinity gradient”

• Medullary portion of CD is permeable to water but not to NaCl

• Water will pass (osmosis) from less concentrated ECF thus causing urine itself to become more concentrated

countercurrent multiplier

• ability of CD to concentrate urine depends on salinity gradient of the renal medulla created by nephron loop → continually recaptures salt and returns it deep into medullary tissue as follows

  • thin descending segment permeable to water ( not salt) so urine becomes very concentrated at Low end of loop

  • Thick ascending segment impermeable to water and actively transports Na+, K+ and Cl- into ECF to maintain high concentration here, while urine becomes very dilute at top of loop Thick ascending

  • Key: the 2 limbs of nephron loop are close enough to influence each other through positive feedback relationship → ability to maintain the salinity gradient

role of urea

• contributes about 40% to the high osmolarity (concentration) deep into the medulla

  • lower end of CD slightly permeable to urea → diffuses out into ECF of renal medulla → some enters descending thin segment of nephon loop → travels through thick ascending loop and DCT which are both impermeable to urea → returns to CD along with new urea continually being added to glomerular filtrate

countercurrent exchange system

• formed by vasa recta

  • provide blood/oxygen supply to renal medullary tissue but do not remove NaCl from medulla (which would destroy salinity gradient role→ prevent ability of CD to concentrate urine)

  • Need their own countercurrent exchange system

• Descending capillaries (into medulla)

  • water diffuses out of blood while NaCl diffuses into blood

• Ascending capillaries (out of medulla) ]

  • water diffuses into blood, while NaCl diffuses out of blood → return the salt back to the ECF of renal medulla

composition and properties of urine

• appearance

  • almost colorless to deep amber; yellow colour due to urochrome from breakdown of hemoglobin (RBC’s)

• Odor: as it strands, bacteria degrade urea to ammonia

• Specific gravity

  • density or urine ranges from 1.000-1.035, affected by

• Osmolarity: (blood = 300 moms/L) = “concentration”

  Ranges from 50 mOsm/L to 1,200 mOsm/L (dehydration)

• PH ranges → 4.5 -8.2 usually ± 6.0

• Chemical composition: 95% water, 5% solutes

  • most abundant = urea, NaCl, KCl, creatinine, uric acid, phosphates, sulfates, Ca, Mg,etc.

urine volume

• normal volume → -1 to 2 L/day

• Polyuria → >2L/day

• Oliguria → <500 mL/day

• Andria → -0 to 100 mL

azotemia

will result when urine output drops below 400 mL/day → body cannot maintain safe, low concentration of wastes in blood plasma

Diuretics

• effects

  • increase urine outpu

  • Decrease blood volume

• Uses

  • drugs for hypertension and congestive heart failure

• Mechanisms of action

  • increase GFR (e.g. caffeine)

  • Decrease tubular reabsorption (e.g. alcohol decreases ADH, drugs inhibit sodium reabsorption)

Total body water for 150 lb person

• 40L

• 65% ICF

• 35% ECF

  • 25% tissue (interstitial) fluid

  • 8% blood plasma and lymph nodes

  • 2% transcellular fluid (= everything else: CSF synovial fluid, etc.)

water movement in fluid compartments

electrolytes play principal role in water distribution and total water content

water gain

• metabolic water (200 mL/d)

  • from aerobic metabolism

  • From dehydration synthesis reactions

• Performed water

  • ingesting in food (700 mL/d) and drink (1600 mL/d)

Water loss

• routes of loss

  • urine feces expired breath sweat, cutaneous transportation (diffusion → evaporation thru skin)

• Loss varies greatly with environment and activity

  • respiratory loss: increase with cold, dry air or heavy work

  • Perspiration loss: increase with hot humid air or heavy work

Insensible water loss

breath and cutaneous transportation

Obligatory water loss

Breath cutaneous transportation, sweat, feces, minimum urine output (400 ml/day)

regulation of fluid intake

• dehydration

  • decrease blood volume and pressure

  • Increase blood osmolarity

thirst mechanism

• stimulation of “thirst center” (in hypothalamus)

  • angiotensin II: produced in response to decrease blood pressure

  • ADH: produced in response to increase blood osmolarity

  • Hypothalamic osmoreceptors: signal in response to increase ECF osmolarity

• Inhibition of salivation

  • thirst center sends sympathetic signals to salivary glands

regulation of output

• only control over water output through variations in urine volume

  1. By controlling Na+ reabsorption in nephron (changes volume of urine)

     • as Na+ is reabsorbed or excreted water follows it

  2. By action of ADH (changes concentration of urine)

     • ADH secretion (as well as thirst center) stimulated by hypothalamic osmoreceptors in response to dehydration

     • Aquaporins synthesized in response to ADH

Disorders of water balance

1. Fluid deficiency

2. Fluid excess

Fluid deficiency

1. Volume depletions (hypovolemia)

   • total body water decrease, osmolarity normal (lose water + solute)

   • E.g. hemorrhage, severe burns, chronic vomiting or diarrhea

2. Dehydration

   • total body water decrease, osmolarity rises (lose water not solute)

   • E.g. lack of drinking water, diabetes, profuse sweating, diuretics

   • Infants more vulnerable (1. High metabolic rate demands high urine excretion, 2. Kidneys cannot concentrate urine effectively, 3. Greater ratio of body surface to mass)

   • Affects all fluid compartments

   - most serious effects (both 1+2) are circulatory shock neurological dysfunction and infant mortality

how dehydration affects all fluid compartments

1. Profuse sweating produced by

2. Capillary filtration through sweat glands

3. Blood volume and pressure drop, osmolarity rises

4. Blood absorbs tissue fluid (ECF) to replace loss through sweat glands Blood

5. Fluid pulled from ICF to replace loss to ECF

   • 1L sweat: 300 mL from ECF, 700mL from ICF

fluid excess

• volume excess

  • both Na+ and water retained, ECF isotonic (some concentration as ICF)

  • E.g. aldosterone hypersecretion

• Hypotonic hydration

  • more water than Na+ retained or ingested, ECF hypotonic (less concentrated than ICF) - can cause cellular swelling

• Most serious effects are pulmonary and cerebral edema

electrolytes functions

• chemically reactive in metabolism, determine cell membrane potentials, osmolarity of body fluids and water content/distribution

• Major cations

  • Na+, K+, Ca2+, H+

• Major anions

  • Cl-, HCO-3, PO43-

sodium functions

• membrane potentials

• Accounts for 90-95% of osmolarity of ECF

• Na+ - K+ pump

  • (exchanges intracellular Na+ for extra cellular K+)

  • Cotransport of other solutes (glucose)

  • Generates heat

• NaHCO3 has major role in buffering pH

sodium imbalances

• hypernatremia

  • plasma sodium >145 mEq/L

  • From IV saline

  • Water retention hypertension and edema

• Hyponatremia

  • plasma sodium <130 mEq/L

  • Losing large amounts of electrolytes via sweat and / or urine than replacing them with just water

  • Quickly corrected by “automatic” excretion of excess water

potassium functions

• most abundant cation of ICF

• Determines intracellular osmolarity

• Membrane potentials (with sodium)

• Na+ - K+ pump

potassium imbalances

• most dangerous of all electrolyte imbalances

• Hyperkalemia effects depends on rate of imbalance

  • if concentration rises quickly (e.g. crush injury), the sudden increase in extra cellular K+ makes nerve and muscle cells abnormally excitable (→ cardiac arrest)

  • If slow onset it inactivates voltage gated Na+ channels nerve and muscle cells become less excitable

• Hypokalemia

  • sweating chronic vomiting or diarrhea, laxatives

  • Nerve and muscle cells less excitable

  • Muscle weakness, loss of muscle tone decrease reflexes arrthymias

chloride functions

• ECF osmolarity

  • most abundant anions in ECF

• Stomach acid

  • required in formation of HCl

• Chloride shift

  • CO2 loading and unloading in RBC’s

• PH

• - major role in regulating pH

chloride imbalances

• hyperchloremia

  • result of dietary excess or IV saline Water retention

• Hypochloremia

  • result of hyponatremia

• Primary effects

  • pH imbalance

Calcium functions

• skeletal mineralization

• Muscle contraction

• Second messenger

• Excytosis

• Blood clotting

calcium imbalances

• hypercalcemia

  • due to alkalosis, hyperparathyroidism, hypothyroidism

  • Decrease membrane Na+ permeability, inhibits depolarization

  • Concentrations >12 mEq/L causes muscular weakness depressed reflexes, cardiac arrhythmias

• Hypocalcemia

  • due to vitamin D decrease diarrhea preganacy acidosis lactation hypoparathyroidism hyperthyroidism

  • Increase membrane Na+ permeability causing nervous and muscular systems to be abnormally excitable

  • Very low levels result in tetanus, laryngospasm, death

Phosphates functions

• concentrated in ICF as

  • phosphate (PO4-3) monohydrogen phosphate (HPO4 2-)

• Components of nucleic acids, phospholipids, ATP, GTP, cAMP

• Activates metabolic pathways by phosphorylation enzymes

• Buffers pH

phosphates homeostasis

• renal control

  • if plasma concentration drops, renal tubules reabsorb all filtered phosphate

• Parathyroid hormone

  • increase exertion of phospahate

• Imbalances not as critical

  • body can tolerate broad variations in concentration of phosphate

acid base balance

• important part of metabolic homeostatis

  • metabolism depedns on enzymes and enzymes are sensitive to pH

• normal pH range of ECF is 7.35 to 7.45

• challenges to acid-base balance

  • metabolism produces lactic acids, phosphoric acids, fatty acids, ketones and carbonic acids

acids

• strong acid ionize freely, markedly lowering pH (raise H+ concentrations in solution) e.g. HCl

• weak acids ionize only slightly; e.g. H2 CO3

bases

• strong bases have a strong tendency to bind H+ markedly raising pH (lower H+ concentration in solution) e.g. OH-

• weak bases bind less of the available H+

buffers

• resist chnages in pH

• convert strong acids and bases to weak ones

chemical buffers

• reactions that restore normal pH in protion of body within fractions of a second

• bicarbonate, phosphate and protein systems

• each buffer has an optimum pH at which to function

physiological buffers

• system that controls output of acids bases or CO2

• A. urinary system buffers greatest quantity of acid/base, but takes several hours or days to exert. its effect

• B. respiratory system buffers within minutes but cannot alter pH to same degree as urinary system

bicarbonate buffer system

• solution of carbonic acid and bicarbonate ions

  • CO2 + H2O ←→ H2 CO3 ←→ HCO3- + H+

• reversible reaction important in ECF

  • CO2 + H2O → H2CO3 → HCO3- + H+

  • lowers pH by releasing H+

  • CO2 + H2O ← H2CO3 ← HCO3- + H+

  • raises pH by binding H+

• functions with respiratory and urinary systems:

  • to lower pH kidneys excrete HCO3-

  • to raised pH, kidneys and lungs excrete CO2

  • optimum pH is 6.1

  • direction determined by Law of Mass Action

phosphate buffer system

• H2PO4- ←→ HPO42- + H+

  • as in the bicarbonate system, reactions that proceed to the right release H+ and decrease pH, and those to the left increase pH

• important in the ICF and renal tubules

  • where phosphate are 1) more concentrated and 2) function closer to their optimum pH of 6.8

  • contant production of metabolic acids creates pH values from 4.5 to 7.4 in the ICF avg. 7.0

protein buffer system

• more concentrated than bicarbonate or phosphate system especially in the ICF

• accounts for 75% of buffering ability of the body fluids

• ability to buffer due to certain side (R-) groups of the amino acid residues

  • acidic side groups can release H+ E.g. -COOH → -COO- H+

  • amino side groups can bind H+ i.e. -NH2 + H+ → -NH3+

respiratory control of pH

• collaborates with bicarbonate system

  • CO2 + H2O → H2CO3 → HCO3- + H+

  • lowers pH. by releasing H+

  • CO2 (expired) + H2O ← H2CO3 ← HCO3- + H+

  • raises pH by binding H+

• increase CO2 and decrease pH stimulate pulmonary ventilation, while an increase pH inhibits pulmonary ventilation

renal control of pH

• most powerful buffer system (but slow response)

• renal tubule secret H+ into tubular fluid most of it binds to bicarbonate, ammonia and phospahte buffers and is then excreted in urine (both bound and free form of H+)

• kidneys are only means of actually expelling H+ from the body directly

limiting pH

• tubular secretion of H+ (step 7)

  • continues inly with a concentration gradient of H+ between tubule cells and tubular fluid

  • if H+ concentration increase in tubular flud, lowering pH to 4.5 (“the limiting pH”) secretion of H+ stops

• this reaching of the limiting pH is prevented by chemical buffers in tubular fluid

  • bicarbonate system

  • Na2HPO4 (dibasic sodium phosphate) + H+→ NaH2PO4 (monobasic sodium phosphate) + Na+

  • ammonia (NH3), from amino acid catabolism, reacts with H+ and Cl- → NH4 Cl (ammonium chloride)

acid base and potassium imbalances

• acidosis

• alkalosis

acidosis

• H+ difuses into cells and drives out K+ elevating K+ concentration in ECF

• H+ buffered by protein in ICF, causing membrane hyperpolarization, nerve and muscle cells are harder to stimulate, CNS depression (from confusion to death)

alkalosis

H+ diffuses out of cells and K+ difuses in membranes depolrized nerves overtsimulate muscles causing spasms, tentany, convulsions, respiratory paralysis

disorders of acid base balances

• respiratory acidosis

• respiratory alkalosis

• metabolic acidosis

• metabolic alkalosis (rare)

respiratory acidosis

rate of alveolar ventilation falld behing CO2 production

respiratory alkalosis (hyperventilation)

CO2 eliminated at faster rate than it is being produced

metabolic acidosis

increase prodcution of organic acids (lactic acid in anaerobic fermentation, ketones in alcoholism and diabetes) acidic drugs (asprin), loss of base (chronic diarrhea, laxative overuse)

metabolic alkalosis (rare)

overuse of bicarbonates (antacids) loss of acid (chronic vomiting)

compensation for imabalances

• resiratory system adjusts ventilation (fast, but limited compensation)

  • hypercapnia (increase PCO2) stimulates pulmonary ventilation, while hypocapnia reduces it

  • good for correcting pH imbalnaces due to elevated PCO2 (e.g. after asthmatic attack or hyperventilation)