Renal System

• 1. Regulation of water, inorganic ion balance, and acid-base balance.
• 2. Removal of metabolic waste products from blood and excretion in the urine.
• 3. Removal of foreign chemicals from teh blood and their excretion in the urine.
• 4. Gluconeogenesis (synthesize glucose from amino acids)
• 5. Production of hormones/enzymes:
• Erythropoitin which controls erythrocyte production.
• Renin, an enzyme that controls the formation of angiotensin and influences blood pressure and sodium balance.
• Activates Vitamin D3 to move calcium in from GI tract.

Juxtamedulary nephrons sit close to the medulla and the capillary beds and tubules go deep into the medulla. The medulla has 300-1200 mOsM.

Cortical nephrons are mostly in the cortex which has 300 mOsM and only a small portion of tubule enters the medulla.

H2O moves by diffusion (osmosis) through aquaporins.

• Million filtering units per kidney.
• Filter 20-25% cardiac output at any given time.
• Portal system.
• Can regulate pressure through either afferent or efferent arterioles.

• Bowman's capsule = 180 L/day @ 300 mOsMoles (isoosmotic with cells, absorbing H20)
• End of Proximal Convoluted Tubule = 54 L/day @ 300 (isoosmotic with cells, absorbing H20)
• End of Loop of Henle = 18 L/day @ 100 (hypoosmotic, removing salts)
• End of Collecting Duct = 1.5 L/day @ 50-1200

• Filtration rate > Excretion rate = net reabsorption
• Filtration rate = Excretion rate = no net reabsorption
• Filtration rate < Excretion rate = net secretion

• Secretion bypasses filtration barrier.
• Filtration and excretion can be measured.

• Constrict afferent arteriole = decreased GFR
• Constrict efferent arteriole = increased GFR
• Dilate afferent arteriole = increased GFR
• Dilate efferent arteriole = decreased GFR

• Intrinsic control by:
• Myogenic response (increase HP, stretch arterioles, smooth muscles contract to control flow. If pressure increases, rate increases to maintain flow.)
• Tubuloglomerular feedback (macula densa, sensor for volume and salt flow in the descending convoluted tubule, activates the juxtoglomerular cells of the afferent arteriole to secrete renin into the blood stream. Renin converts angiotensinogen to angiotensin I which is converted to angiotensin II which is a vasoconstrictor. This increases MAP systemicaly which increases pressure in the kidneys.)

Intense exercise leads to increased vascular resistance (sympathetic tone) which decreases GFR. Afferent arteriole constricts, pressure in tubule decreases, GFR decreases.

Hrmorrhage will increase vascular resistance and decrease GFR. Barroreceptors decrease firing, sympathetics increase firing, afferent arterioles constrict and GFR decreases.

• The kidney's primary functions are to maintain fluid volumes of the body by regulating salt balance and to maintain the osmolarity of the body by regulating water balance.
• GFR is regulated independent of MAP ranging from 80-180 mmHg because of autoregulation.
• Autoregulation can include myogenic responses, tubular-glomerular feedback and reflex feedback.
• Renal blood flow is regulated independent of MAP between 80-180 mmHg by changing the resistance of the renal arteries and arterioles.
• Filtration fraction is the ratio of GFR to renal plasma flow (RPF). In a normal human kidney this is usually 0.2.
• Reabsorption moves filtered solutes from the renal tubule to the blood.
• Reabsorption of solutes occurs predominantly within the PCT. Some reabsorption of Na+, K+ and Cl- also occurs within the TAL. Only 1% of Na+ reabsorption occurs in the DCT and CD and is regulated by aldosterone.
• Most solutes cross the epithelium by secondary active transport with Na+. Urea and Cl- reabsorption is by facilitated diffusion in the distal 1/3 region of the PCT.
• Reabsorption within the PCT occurs iso-osmotically with water following Na+.
• Secretion of organic compounds occurs in the PCT by secondary active transport.
• Secretion of K+ occurs in the DCT and CD in response to increased Na+ delivery or high fluid flow.
• Clearance (C) is the excretion rate of a substance. C equals GFR when the substance is freely filtered but not secreted or reabsorbed. Clearance is comparative because only the net handling of a substance can be determined. Inulin is used as an exogenous standard; creatinine an endogenous standard.
• Two-thirds of the body’s water is in the ICF; one third in the ECF. The ICF and ECF are in osmotic balance.
• The kidneys’ primary functions are (1) to maintain fluid volumes of the body by regulating salt balance and (2) to maintain the osmolarity of the body by regulating water balance.
• Reabsorption and secretion of water and solutes is governed by concentration gradients and secondary active transport.
• Healthy people use hormones to regulate osmolarity (ADH), to regulate K+ (aldosterone), and to regulate volume (ADH, aldosterone, ANF).
• Increased urine excretion above 1mL/min is called diuresis. There are several causes including: water, osmotic and diuretic.
• As a result of metabolism, the body has a net production of acids. The kidneys excrete excess H+ combined with urinary buffers such as phosphate (fixed or titratable acid) and ammonia.
• The kidneys with the lungs maintain the body’s pH by regulating the HCO3-/CO2 buffer pair. The lungs exert an immediate effect by controlling PCO2; the kidneys exert a slower effect by controlling HCO3- and H+ concentration.
• There are four types of acid-base disturbances. They are classified as to the direction of change in pH (acidosis or alkalosis) and by the underlying problem (ventilation or metabolism).

• At transport maximum (Tmax) transporters are saturated.
• There is alinear uptake of glucose using transporters below 300 mg/100mL plasma.

In DM, glucose remains in the tubule which holds water in the tubule and they cannot concentrate urine.

• Excretion (E) = Amount filtered (F) - Amount reabsorbed (R) + Amount secreted (S)
• Can measure E and F but not R or S.

• Kidney can conserve water but can not replenish water.
• Only water excreted by the kidney can be regulated.

Kidney influences TPR.

• Remember:
• CO = SV x HR
• CO = MAP/TPR

• ADH released by posterior pituitary, signalled by high Na+.
• ADH regulates water transport in distal convoluted tubule and collecting duct.
• Aquaporin channels are controlled by ADH (vasopressin).
• Central pathology: Pituitary doesn't generate ADH.
• Nephrogenic pathology: No ADH receptors or no aquaporins.

Diabetes insipidus: No ADH action, urinate 18 L/day.

• Aldosterone is released in response to increased K+ and angiotensin II.
• Renin => ANG I => ANG II => Aldosterone release.

Decreased plasma volume stimulates the hypothalamus, via the posterior pituitary, to release ADH (vasopressin), which stimulates the kidneys to release renin. Renin -> ANG I -> ANG II (controlled by ACE). The adrenal is stimulated to release aldosterone which acts on the kidneys to conserve H2O and Na+.

• The secretion of ADH is inhibited by Osmolarity < 280 mOsM, increased BP, and increased arteral stretch.
• Arterial stretch -> atrial natriuretic factor (ANF) which works on the afferent arterioles for vasodilation to reduce volume by increasing Na+ and water loss.

Water diuresis – decreased osmolarity of plasma and/or increased blood volume leading to decrease in anti-diuretic hormone (ADH) levels.

Osmotic diuresis - osmotically active substance (e.g., glucose) within renal tubule holds H2O so urine can't concentrate.

Diuretics - drugs that increase loss of body water primarily by inhibiting Na+ reabsorption by the renal tubule. Diuretics act at different segments of the renal tubule.

• IV Isotonic NaCl
• Total body water increases -> ECF volume increases -> ICF volume unchanged -> ECF osmolarity unchanged -> ADH secretion decreases

• Diarrhea (isotonic loss)
• Total body water decreases -> ECF volume decreases -> ICF volume unchanged -> ECF osmolarity unchanged -> ADH secretion increases

• Excessive NaCl intake
• Total body water unchanged -> ECF volume increases -> ICF volume decreases -> ECF osmolarity increases -> ADH secretion increases

• Excessive sweating (hypotonic loss)
• Total body water decreases -> ECF volume decreases -> ICF volume decreases -> ECF osmolarity increases -> ADH secretion increases

State in which arterial blood pH is lower than 7.35

State in which arterial blood pH is greater than 7.45

Disorder that lowers the arterial blood pH to < 7.35

Disorder that raises the arterial blood pH to > 7.45

• Intracellular:
• Negatively charged proteins (Hb) trap H+ but do not rid the body of H+.
• 60-70% of body's total buffering capacity.

Extracellular: Bicarbonate HCO3-

Ventillation keeps normal plasma HCO3- = 24 mEq/L

PCT reabsorbs 70-80% HCO3-

Type A secrete H+ in acidosis (acid urine)

Type B secrete HCO3- in alkalosis (basic urine)

• Glutamine converted to NH4+ which converts to NH3 in CD where it combines with H+ and NH4+ is excreted.
• If NH4+ stays in the blood, liver converts it to urea and it shows in blood tests as elevated BUN.

Elevated BUN = kidney problems, collecting ducts aren't working.

• What is pH of arterial blood?
• - normal (pH 7.35-7.45), alkalemia (>pH 7.45, acidemia (<pH 7.35)?

• Is it metabolic or respiratory disorder; acidosis or alkalosis?
• - examine the HCO3- and PaCO2. Normal values are 24 mEq/L for HCO3- and 40 mm Hg for PaCO2. Compensatory mechanisms can not correct acid-base disorders by themselves, change in pH indicates underlying problem as either acidosis or alkalosis.

• What is the compensatory response?
• - metabolic disorders cause changes in ventilation.
• - respiratory disorders change renal net acid excretion.

• Respiratory Acidosis:
• H+ increases, PaCO2 increases, caused by decreased ventilation (lung problem)

• Respiratory Alkalosis:
• H+ decreases, PaCO2 decreases, caused by increased ventilation

• Metabolic Acidosis:
• H+ increases, PaCO2 decreases, caused by decreased bicarbonate (lungs try to blow off CO2)

• Metabolic Alkalosis:
• H+ decreases, PaCO2 increases, caused by increased bicarbonate

• Typically each day the total acid secretion by the kidney includes:
• Reabsorption of filtered HCO3-... 4500 mEq
• Fixed acids produced... 35 mEq
• NH4+ produced... 36 mEq

• Acid input = about 70 mEq/day (fixed acids produced + NH4+ produced)
• Acid output = about 40 mEq/day = pH 7.4 urine