ECF: plasma and interstitial fluid

ICF: fluid in the cells

1. solutes: 

A: nonelectrolytes (glucose)

B: electrolytes

2. suspended particles: blood cells/RBC

3. solvent: water

4. colloid proteins: large proteins (serum albumin, negative charge)

2/3 of body water

-low Na, Cl, bicarb

-high K 

K is the major intracellular electrolyte > determines 50% of osmolality

1/3 of body water 14 L

high Na, Cl, bicarb

low K

Na and Cl makes up 50% of osmolality

1. capillary membrane: barrier to proteins

2. cell membrane: barrier to protein and solutes

3. water flow is unimpeded

1. respiratory: CO2 is metabolic waste product

2. digestive: undigested materials, bacteria, substances excreted into bile

3. urinary: waste products (urea, uric acid, creatinine, ammonia salts), water, toxic molecules, excess ions

1. excretion 

A. end products of metabolism: urea (AA > NH3 > urea), creatinine (muscle creatine), uric acid (nucleic acid), bilirubin (hemoglobin), metabolites of hormones

B. foreign substances: drugs, pesticides, other chemicals

2. homeostasis

A. water balance

B. electrolyte balance

C. acid base balance

3. regulation of arterial pressure

A. renin angiotensin system

4. regulation of erythrocyte production: secretion of EPO by MD cells stimulates RBC production in bone marrow

-stimulated by hypoxia

5. vitamin D metabolism: vitamin D from diet is activated by the kidney to form calcitriol > required for Ca absorption in GI tract

6. gluconeogenesis

-main site is the liver but occurs in the kidney with prolonged fasting

-AA and lactic acid are turned into glucose

consists of the paraventricular and supraoptic nuclei and neurons of the ventral hypothalamus

supraoptic nuclei > hypothalamic hypophyseal tract > posterior pituitary > release of oxytocin and ADH

ventral nucleus > anterior pituitary > TSH, LH, FSH, etc.

25% of cardiac output > filter 20% of the renal plasma flow

25% = renal fraction = portion of total cardiac output that flows through the kidney

20% = amount of plasma that is removed from the blood

2 kidneys

size of a clenched fist

retroperitoneal

no nociceptors in renal tissue

capsule and ureter have nociceptors

nephron = functional unit = 1e6 nephrons in EACH kidney

cortex: outermost layer 

pyramid: bundles of collecting ducts

medulla: formed by the columns > extension of cortex between renal pyramids, passage for blood vessels and nerves to and from the cortex

pelvis: within the renal sinus, collects urine from the pyramids and travels to the ureters

1. cortical: 80-85% > lie ALMOST COMPLETELY in the cortex

2. juxtamedullary: 10-15% > lie in cortex and medulla

ureter: smooth muscle > USES PERISTALSIS

-has nociceptors

urinary bladder: smooth muscle sac > stretch receptors which detect distension

-uterus is on top of the bladder

-urethra: tube from bladder to exterior

-in males the prostate gland surrounds the urethra

1. stretch receptors in the urinary bladder detect distension > sends signals to PNS, spinal reflex

2. PNS = urinary bladder contractions

3. internal sphincter = neck of the bladder = smooth muscle > contractions

4. external sphincter = distal to the neck of the bladder after the prostatic urethra = skeletal muscle > controlled by somatic motor nerves

-control of external sphincter begins at age 2-3

2 kidneys

2 ureters

urinary bladder

urethra

bowman's capsule + glomerulus = filtration apparatus

1. parietal epithelial or capsular cells = make up the bowman's capsule

2. visceral epithelial or glomerular or podocyte cells = surrounds the glomerulus

-bowman's space

-ultrafiltrate = not specific > formed by free flow of solutes which are excluded by size

2nd capillary bed

found ONLY IN THE CORTEX

surrounds tubular elements = PCT/loop/DCT

renal absorption and secretion

3rd capillary bed

LOCATED IN THE MEDULLA

not really a capillary bed > series of porous vascular loops

-surrounds loop of henle and collecting duct

1. concentrates urine

2. brings O2 and nutrients to the tubule

1. filtration: of nutrients and waste from the blood in the glomerulus into bowman's space/tubule

2. reabsorption: tubule returns needed substances into the blood

3. secretion: selected waste products into tubule

4. excretion: urine leaves system

-EXCRETION = FILTRATION - REABSORPTION + SECRETION

1. capillary endothelium = has fenestrations 

2. basement membrane = excludes by negative charge > PRIMARY BARRIER TO FILTRATION

3. podocyte cell processes = filtration slit

brush border cuboidal epithelial cells

lots of microvilli

highly folded basement membrane

transport proteins > reabsorption and secretion

free water movement

flattened cell

few microvilli

few transport proteins > not permeable to solutes

free water movement

glycoprotein cover on luminal membrane

impermeable to water

some transport proteins > permeable to NaCl

specialized for secretion and reabsorption

glycoprotein covering > impermeable to water

junction between thick ascending loop/DCT and the afferent/efferent arterioles

1. macula densa cells: osmoreceptors located on the the wall of the DCT

-secrete EPO

2. juxtaglomerular cells: mechanoreceptors activated by distension located on both afferent and efferent > mostly afferent arteriole

-secrete renin

can talk via paracrines

highly hormonally regulated area 

1. principal cells: Na/K antiporter which reabsorbs Na (and water if possible) and secretes K

2. intercalated cells: control acid/base balance > Na/H antiporter, reabsorb bicarb

stimulus:

1. low BP

2. low Na

3. high K

4. angiotensin 2

released from adrenal cortex

act on principal cells

result:

1. increased Na/K antiporter

2. water reabsorption if possible

stimulus: 

1. low BP

2. high osmolarity

produced in the supraoptic nuclei of the hypothalamus > released from posterior pituitary

acts on principal cells

result:

1. increased aquaporins > allow water to be reabsorbed

2. low urine volume

water

ions (Na, K, Cl) > electrolytes equal to blood

nitrogenous wastes (urea, uric acid, creatinine)
organic molecules (glucose, AA)

NO PROTEINS

osmolality essentially equal to blood (except proteins)

formed via PASSIVE BULK FLOW from the hydrostatic blood pressure

not freely filtered, not secreted, not reabsorbed > EXCRETION = 0

-large charged molecules

freely filtered, not secreted, not reabsorbed > 

EXCRETION = FILTRATION

-inulin: helps measure GFR

freely filtered, not secreted, fully reabsorbed > 

EXCRETION = 0

-nutritional substances, AA, glucose

freely filtered, not secreted, partially reabsorbed >

EXCRETION < FILTRATION

-electrolytes

PHB: hydrostatic blood pressure: 55 mmHg

-pushes fluid OUT of the glomerulus into bowman's space

PHc: capsular hydrostatic pressure: 15 mmHg

-solutes in the bowman's capsule exerts force on glomerulus and pushes fluid IN

Po: plasma oncotic pressure: 30 mmHg

-large proteins in the glomerulus which are not freely filtered > DRAW WATER IN VIA OSMOSIS

outward force - inward force

PHB - (PHC + Po)

55 - (15+30) = 10 mmHg

1. active transport: moves Na out into the blood system > keeps intracellular Na low

-Na/K ATPase on the basolateral membrane

2. passive transport

-water, urea, lipid soluble, nonpolar compounds

3. cotransport = facilitated diffusion: uses the concentration gradient of Na as energy to pass through the luminal membrane into the cell

-Cl, K, glucose, AA

can be caused by saturation of carrier protein or energy source required (contransport or ATP)

AMT IN FILTRATION > REABSORPTION RATE

blood glucose > 200 mg/dL

-Na/glucose cotransporter on the PCT luminal membrane is saturated > glucose left in the urine and gets excreted > water stays with the glucose > diuresis

1. polydipsia: excessive thirst

2. polyphagia: excessive hunger

3. polyuria: excessive urination

1. glomerulus: osmolarity ultrafiltrate = osmolarity blood

2. PCT: reabsorption/secretion but also unimpeded water movement > 65% water reabsorbed > also isoosmotic

3. descending loop: unimpeded water movement, not permeable to solutes

-osmolarity = 1200 at the bottom of the loop

4. ascending loop of henle: reabsorption and water is impeded

A. passive transport on thin ascending limb decreases osmolarity to 400

B. active transport on thick ascending limb decreases osmolarity to 100

5. late DCT and collecting duct: hormonally regulated

osmolarity = 100

loop of henle = countercurrent multiplier = sets up osmotic gradient

vasa recta = countercurrent exchanger = maintains osmotic gradient

series of porous vessels > NOT A CAPILLARY BED

sluggish blood flow > ONLY RECEIVES 10% OF RBF

ascending and descending vasa recta matches with the opposite loop of henle

25% of CO filtered by the kidney > 180L of ultrafiltrate produced a day

-65% water reabsorbed in PCT

-15% in the descending loop

-19% in the late DCT and collecting duct

1% LOST = 1.8 L/day

normal is 100

can go lower (50) and higher (max 1200)

produced in the adrenal cortex

1. bind to aldosterone receptor on principal cells of the late DCT and collecting tubule

2. increases synthesis of 

A. Na/K antiporter on luminal and Na/K ATPase on basal

total filtration produced by both kidneys

normal GFR at 120mmHg systemic pressure = 125 mL/min or 180 L/day > 180 L filtrate produced everyday

CO = 5 L

body water volume = 42 L

GFR = NFP (Fc)

Fc = Kf = filtration coefficient: intrinsic permeability of the glomerular capillary and glomerular surface area available for filtration

Fc = capillary permeability * filtration surface area = 12.5 mL/min/mmHg = normal

-ways to change: inflammation of endothelium, dead nephrons

only concerned with kidney homeostasis > WANT CONSTANT GFR NO MATTER WHAT

1. myogenic control

2. tubuloglomerular feedback

3. prostaglandin controls

intrinsic ability of vascular smooth muscle (afferent and efferent arterioles) to respond to pressure change

FLOW IS DIRECTLY RELATED TO RADIUS AND PRESSURE

-increase pressure > increase flow > arteriole stretches > intrinsically able to contract > reduced radius > normal flow

communication via paracrines between JG and MD cells

1. high NaCl or high flow in DCT > alerts the MD cells > release paracrines (adenosine or ATP) to the afferent arterioles > causes vasoconstriction

1. low NaCl or low flow in DCT > alerts the MD cells > release LESS PARACRINES and NO > cause vasodilation of the afferent arteriole

2. JG cells respond to low BP at AA, SNS, increased MD paracrine > causes renin release > eventually angiotensin 2 which has effects to systemic vasoconstriction

3. afferent arteriole is protected by NO > stays vasodilated

4. efferent arteriole is vasoconstricted > blood stays in the glomerulus > longer time to filter and will get more NaCl into the ultrafiltrate

PG produced locally during pathophysiological conditions (extreme drop in BP that alerts baroreceptors to cause systemic vasoconstriction)

-released locally and causes vasodilation of the afferent arteriole > keeps blood flow moving into the kidney > prevents severe renal ischemia > has small effect on GFR

concerned with ECF, BV/BP and osmolality > TOTAL BODY HOMEOSTASIS

1. renin-angiotensin system

2. atrial natriuretic hormone

3. sympathetic nerves and circulating epi

renin release by JG cells mediated by extra renal control

-low BP is detected by the hypothalamus baroreceptors > causes kidney JG cells to release renin > eventually leads to the 4 effects of angiotensin 2

overrides local autoregulation of GFR in times of extreme blood loss

-intense SNS tone > systemic circulation to shunt blood to vital organs (skeletal muscle, cardiac muscle and brain)

-can lead to vasoconstriction of the afferent arteriole which leads to kidney failure > decreased GFR > increased waste products left in the kidney > decreased urine production

1. carbonic anhydrase inhibitor

2. osmotic agents/nonreabsorbable solute

3. loop diuretics

4. thiazides

5. aldosterone antagonists

6. ADH antagonists

7. Na flux inhibition/Na channel blockers

mannitol

 give to patient > mannitol does not have a transporter > freely filtered but not reabsorbed at all > stays in the lumen > water movement from blood to lumen by osmosis

diamox/acetazolamide

permanently inhibits CA (bound and cytoplasmic) in the PCT > less H+ intracellularly > less Na/H antiporter secretion > more Na is able to stay in the lumen > water moves by osmosis from blood to lumen

uses:

1. metabolic alkalosis: CA inhibition also stops bicarb production

2. glaucoma

3. acute mountain sickness

forerunner of modern diuretics!

furosemide

blocks the Na/2Cl/K symporter on the thick ascending loop of henle > more Na, Cl, K in the lumen > Na travels through the Na/K antiporter on the luminal membrane which causes K secretion > Na, K, Cl in the lumen > water moves by osmosis

K wasting > hypokalemia is a side effect

hydrochlorothiazide

inhibits the Na/Cl symporter on the luminal side in the early DCT > forces Na to use the Na/K antiporter which causes hypokalemia

1. convey tubular fluid to the renal pelvis

2. finalize urine composition in terms of

A. solute concentration: Na and bicarb

B. water volume

C. pH: hydrogen ion secretion and bicarb reabsorption

lithium

blocks aquaporin production on late DCT/collecting tubule for the principal cells 

K sparing

spironolactone

blocks Na/K antiporter on the principal cells 

K sparing

triamterene and amiloride

blocks entry to Na into Na channels

K sparing

ADH antagonist

aldosterone antagonist

Na flux inhibitors

loop diuretics

thiazides

history and physical exam

1. urinalysis

2. serum urea (BUN, blood urea nitrogen) level

3. serum creatinine

both are freely filtered from glomerulus to urine

secretion into urine

HIGHER CONCENTRATION IN URINE COMPARED TO ULTRAFILTRATE

made in the liver

disposes of ammonia from protein metabolism 

good test for renal function > cleared by the kidneys

NORMAL: 8-25 mg/dL or 2.9-8.9 mmol/L

PANIC: over 100 mg/dL

increased in nitrogenous waste products can be caused by:

1. impaired kidney function

2. increased protein catabolism

A. increased protein in diet

B. severe stress (MI, fever)

C. upper GI bleed (proteins present in blood)

D. severe dehydration (lack of fluid to excrete waste products)

decreased BUN: 

1. lack of protein

2. severe liver disease: urea synthesized by the liver

3. overhydration due to increased ADH

-non protein waste product of creatine phosphophate metabolism by skeletal muscle tissue

-continuous production

-freely filtered by glomerulus > not reabsorbed or secreted (in small amounts) so it is good for GFR estimate

renal dysfunction > cannot remove the creatinine > serum creatinine increases

NORMAL ADULT MALE: 0.8-1.4 mg/dL

NORMAL ADULT FEMALE: 0.6-1.1 mg/dL

NORMAL CHILDREN: 0.2-1.0 mg/dL

PANIC: 10 mg/dL in non-dialysis patients

amt depends on SKM amt

as Scr goes up, GFR goes down

PANIC: 10 mg/dL creatinine > 10% of normal GFR = 12.5 mL/min > 10% NEPHRONS ARE WORKING

10 mg/dL = ESRD

-useful and inexpensive to measure renal dysfunction

-more specific and sensitive compared to BUN 

DOES NOT RISE UNTIL AT LEAST 50% OF NEPHRONS ARE DESTROYED

increased

1. impaired renal dysfunction

2. chronic nephritis

3. urinary tract obstruction

4. muscle diseases

5. congestive heart failure

6. drugs that block creatinine secretion > creatinine is secreted a little: triamterene

decreased: little clinical significance

1. elderly

2. small stature

3. decreased muscle mass

4. inadequate dietary proteins

NORMAL: around 10

PANIC: values above 10

15 = renal failure

volume of plasma cleared of X per unit time

plasma clearance (mL/min) = urine volume (mL/min) * (conc X in urine/conc X in plasma)

-used to approximate GFR > need timed urine sample and blood sample

NORMAL: 90-120 mL/min for young adults

-value will fall by 0.5 every year after 20 yrs 

characterized by:

1. rapid deterioration of renal function > ACUTE NOT CHRONIC

2. increased BUN and Scr

3. inability to maintain fluid and electrolyte balance and excrete nitrogenous wastes

4. death of nephron and sloughing of tubular epithelial cells into urine

sxs: initially none but can have sxs if not treated

1. uremia (clinical syndrome associated with azotemia): fatigue, malaise, NV, altered mental status, anorexia

2. arrhythmias and seizures from electrolyte imbalance

3. diffuse abdominal pain

Lab findings:

1. azotemia

2. hyperkalemia

3. hyperphosphatemia

4. hypocalcemia

5. anemia and platelet dysfunction

NORMAL URINE OUTPUT: 1-1.8 L/day

1. anuria: less than 50 mL/day

2. oligourina (diminished urine volume): 50-240 mL/day

3. non-oliguria: greater than 450 mL/day

1. prerenal azotemia

2. intrinsic renal failure

3. postrenal azotemia

PROBLEMS WITH BLOOD COMING INTO THE KIDNEY > RENAL HYPOPERFUSION

1. extreme blood loss > intravascular volume depletion

2. fluid loss

3. cardiac failure > hypotension

4. cirrhosis: blood pools at liver and doesn't reach kidney

5. drugs (NSAIDS)

6. stenosis of renal artery

7. structural lesions on renal arteries

1. decreased GFR

2. increased BUN/Scr > 20

3. UNa < 20

4. FeNa < 1%

5.  > 1.5 urine/serum osmolality

BLOCKAGE OF URINE PASSAGE AFTER KIDNEYS

1. obstruction of the ureters

2. stones in ureter

3. tumor/malignancies of ureter

-most often bilateral obstruction

4. prostatic enlargement/hypertrophy > can block the ureter

1. BUN/Scr: 10-20 still slightly elevated

2. UNa: greater than 40

3. FeNa: variable > depends on severity

4. urine/serum osmolality: < 1.5

1. inflammatory > interstitial nephritis (10%) and acute glomerulonephritis (5%)

2. tubular necrosis > ischemia (50%), toxins (35%)

50% ischemia: thrombosis, hypoperfusion

35% toxins: exogenous or endogenous agents

exogenous: 

1. aminoglycosides

2. amphotericin B

3. radiographic contrast media

4. cisplatin

5. overdose of acetaminophen

endogenous:

1. myoglobin (rhabdomyolysis)

2. hemoglobin

3. hyperuricemia: uric acid

4. bence jones proteins (multiple myeloma): increased Ig monoclonal globulin proteins

1. BUN/Scr: 15

2. UNa: > 40

3. urine/serum osmolality: < 1.3 > lose the ability to concentrate urine so urine osmolality decreases

4. casts > cells of the PCT or loop of henle or DCT are damaged > slough off into urine

1. drugs > 70%

1. penicillins and cephalosporins > antibiotics

2. sulfonamides and sulfa based diuretics > diuretics

3. NSAIDS

4. rifampin

5. phenytoin

6. allopurinol: misc

7. neuropsychs

2. infectious diseases

1. streptococcal 

2. CMV

3. histoplasmosis

3. immunologic disorders

1. intrinsic autoimmune disorders

1. fever

2. rash

3. arthralgia

4. hematuria

5. proteinuria

6. urinary WBC

better prognosis compared to tubular necrosis > can get rid of the inflammation

1. autoimmune disorder especially in the glomerular basement membrane that causes destruction of glomerulus (extreme)

1. goodpasture's syndrome

2. wegener's granulomatosis

3. lupus

1. htn

2. edema

3. hematuria

progressive loss of renal function over months to years > chronic injury that results in irreversible loss of nephrons

classified in 5 stages: stage 5 is ESRD

1. systemic diabetes: 50%

2. htn

3. glomerulonephritis

4. polycystic kidney disease: inherited disorder in males

1. azotemia over many years > causes uremia > uremia (clinical syndrome associated with azotemia): fatigue, malaise, NV, altered mental status, anorexia

2. can be initially asymptomatic

3. proteinuria

4. hyperkalemia if GFR is less than 10 mL/min

5. metabolic acidosis: inability to excrete acids

6. bilateral small kidneys

7. anemia: bruise easily, metallic taste, breath odor

8. shortness of breath

9. nocturia (night urination)

10. impotence

11. electrolyte imbalance: numbness, leg cramps

12. increased waste products: irritability, inability to concentrate

1. increased BUN/Scr

2. isosthenuria: inability to concentrate urine above isoosmotic (300)

3. decreased GFR

4. casts

1. electrolyte imbalance: Na and water excess, hyperkalemia if GFR is less than 10, metabolic acidosis, hyperphosphatemia, hypocalcemia

2. hypertension

3. pericarditis

4. CHF

5. anemia

6. coagulopathy: platelet dysfunction

7. renal osteodystrophy: bone disorder

1. flank pain: distension of ureter, renal pelvis or capsule

2. hematuria

3. fever

4. absent or decreased urine production/anuria: bi or unilateral obstruction of kidney

5. azotemia: bi or unilateral obstruction of kidney

1. 75% contain Ca > idiopathic hypercalciuria with hyperuricosuria and hyperparathyroidism

2. uric stones: hyperuricosuria, gout, excess purine intake (organ meat products)

3. struvite stones: made up of magnesium, ammonia and phosphate salts > urinary tract infection by urease producing organisms

1. defective AA transport > cystinuria

2. dehydration

3. high protein diet

4. high Na diet

ways to stop stone formation

1. fluids

2. citrate

3. magnesium

4. dietary fiber

for small stones

1. fluids

2. bed rest

3. analgesia

1. hydronephrosis and permanent renal damage due to obstruction

2. infection or abcess formation 

3. renal damage due to repeated stones

4. htn from renin production by obstructed kidney