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Renal Physiology

Renal dynamics have a major influence on the volume and composition of extracellular (ECF) and intracellular (ICF) fluid compartments


Renal Physiology

Water is responsible for 50% to 70% of body weight
o Approximately 2/3 of the body’s total body water in intracellular
o Approximately 1/3 is extracellular.
The extracellular compartment is divided into:
• Interstitial fluid – fluid between cells
• Plasma – aqueous component of blood


Renal Physiology

ECF provides the immediate environment around the cell. In large part, the composition of the fluid in the extracellular compartment is responsible for the health of individual cells.
The kidneys play a crucial role in regulating the composition of the ECF


Functions of the Kidney

A. Excretion of metabolic waste products /foreign chemicals
B. Regulation of H20 / electrolyte balance
C. Regulation of body fluid osmolarity
D. Regulation of arterial pressure by:
o Varying levels of Na+ /H20
o The direct and indirect effects of the Rennin – angiotensin-aldosterone system
E. Regulation of acid / base balance through excretion of “fixed” acids and regulation of ‘buffer stores” (HCO3-)
F. Regulation of erythrocytes production via erythropoietin by peritubular capillary cells
G. Influences Calcium / Phosphorus / Vitamin D metabolic pathways


Gross Anatomy

A. Renal Cortex
B. Renal Medulla – hyperosmolar – approximately 1200mOsm/L
C. Renal Papilla


The Nephron

The functional unit of the kidney. There are approximately 1 million nephron units per kidney.


The Glomerulus

1. Capillary network surrounded by Bowman’s capsule
2. An ultra filtrate of blood is produced by the glomerulus
3. The glomerulus possesses both afferent and efferent arterioles


The Renal Tubules

1. Tubular structures lined with epithelia cells which function in reabsorption / secretion of water, electrolytes, and waste products, etc.
2. The glomerular filtrate volume is reduced, and content altered by reabsorption /secretion
3. Specific areas of tubules have specific functions. Tubules are divided into:
a. Proximal convoluted tubules
b. Proximal straight tubules
c. Thin descending limb of the loop of Henley
d. Thick ascending limb of the loop of Henley
e. Early distal tubule and Macula densa
d. Distal convoluted tubule
f. Collecting Duct
4. Peritubular capillary beds are the second capillary network in the unusual arrangement of two capillary beds in series


Renal blood flow

Approximately 22% of cardiac output (≈1200cc/min)


Sequence of Renal Blood Flow:

Renal arteries branch into:
Afferent arterioles -> Glomerular capillaries (1st capillary network) -> Efferent arterioles -> Peritubular capillaries (2nd capillary network, arranged in series) -> Venous capillaries


The Juxtaglomerular Apparatus

o Tuboglomerular feedback: the juxtaglomerular apparatus and macula densa play important roles in regulating renal blood flow
o Myogenic hypothesis
o Renal autoregulation is not dependent on the autonomic nervous system. Transplanted kidneys demonstrated autoregulation of blood flow


The Juxtaglomerular Apparatus

The JG apparatus’ close association with the distal renal tubules and the vascular pole of the nephron places it in an ideal position to senses the composition of the glomerular filtrate in the distal renal tubule and to make adjustments to the vascular tone of the afferent and efferent arterioles adjusting blood flow across the glomerulus and thereby producing the ideal volume of glomerular filtrate (not too much, not too little).


The Juxtaglomerular Apparatus

If overall blood flow to the kidney is inadequate, larger quantities of renin are released by the kidney, which under normal circumstances, will result in increased renal blood flow via the renin-angiotensin-aldosterone system (Na retention>increasing blood volume>increasing preload> cardiac output>renal blood flow AND increasing system vascular resistance> increasing blood pressure>promoting increased renal blood flow)


Glomerular Filtration

o 20% of serum presented to glomerulus is filtered resulting in production of large volumes of glomerular filtrate
o The “filtrate” is identical to serum plasma with the exception of the lack of protein and other larger substances carried in the serum plasma


Glomerular Filtration - Pathophysiology

Diseases which damage glomerular capillary membrane such as diabetes, HTN (hypertension), glomerulonephritis, UTI (urinary tract infection), may cause proteinuria - protein leakage into the urine; nephrotic syndrome is a condition in which there is leakage of very large amounts of protein from the glomerulus resulting in massive proteinuria. This results in hypoproteinemia and often generalized edema.



glomerular filtration rate in ml /minute



In measuring GFR, an ideal substance used in the measurement would be freely filtered, but not reabsorbed or secreted by tubules; In research laboratories Inulin is used in this measurement. By using the Fick principle, if you know the serum concentration of inulin, and you know the urine concentration, one can calculate how much inulin has been filtered across the glomerulus



Serum Creatinine and BUN (blood urea nitrogen) blood levels give an estimate of GFR. Small rises in serum creatinine concentration may indicate impairment or loss of function of the majority of nephrons units.


Creatinine Clearance

Is a commonly used measurement to assess GFR. Serum creatinine is filtered by the glomerulus and filtrate concentrations are minimally altered by the tubules. It is a convenient, but somewhat problematic substitute for inulin.


States that alter GFR

Diseases of glomerulus that reduced the total filtering area available, (loss of glomeruli) or reduce or increase permeability of the glomerular capillary membrane will alter GFR


States that alter GFR

Starling Forces in the kidney alter GFR:
- Increases in pressure in Bowman’s capsule decreases GFR (ex. Urinary tract obstruction)
- Increases or decreases of glomerular hydrostatic pressure affects glomerular filtrations (ex. sympathetic nervous stimulation, changing angiotensin II levels, heart failure, post kidney venous obstruction, arteriosclerosis of the renal artery, excessive blood flow to capillaries)


Starling Forces in the kidney alter GFR

a. Increasing afferent arteriolar resistance – GFR decreases

b. Increasing efferent arteriolar resistance – GRF increases

c. Arterial pressure; Autoregulation 75 –160mm Hg; if renal blood flow and GFR are too high, the macula densa of the juxtaglomerular apparatus release vasoactive substances that constricts afferent arterioles

d. Hormones and other vasoactive substances- examples:
-Angiotensin II constricts efferent vessel to a greater degree than afferent vessels
- Prostaglandins E2 and I2 – cause vasodilatation of afferent arterioles

e. Sympathetic nervous system – constricts afferent arterioles (higher number of alpha receptors) to a greater degree than efferent arterioles

f. Plasma oncotic pressures changes may cause more minor changes in GFR –examples: multiple myeloma (very high serum protein state), liver failure (cirrhosis-low serum protein states), nephrotic syndrome, large burns (loss of albumin)


Tubular Processing of Glomerular Filtrate Sequence

- Glomerular filtrate
- Proximal renal tubules
- Loop of Henle
- Distal renal tubules
- Medullary Collecting Ducts


Processing of Glomerular Filtrate

In the course of moving through the renal tubules, some substances are reabsorbed from the tubule lumen, and other are secreted into the tubule lumen by:
- Simple diffusion
- Active transport – K+, H+, amino acids, glucose, HC03-, Ca+, Na+, Mg+, many organic acids and organic bases


Processing of Glomerular Filtrate

Reabsorption rates differ for different substances:
- Glucose and Amino acids are completely reabsorbed
- Pathophysiology: Glucose reabsorption demonstrates saturate kinetics. All glucose is reabsorbed at plasma levels below 350mg/dl. Beyond this level, transporters are saturated and glucose then appears in the urine –glucosuria
- Na+, Cl-, HC03 – are highly reabsorbed, but the rates may change depending of the body’s needs
- Urea, Creatinine – poorly reabsorbed


The Proximal Tubule

- Highest capacity for reabsorption
- 65% of filtered H20, Na+, Cl-, K+, are reabsorbed in proximal tubules
- Conserves substances needed by body
- Less permeable to waste products such as urea


Loop of Henle

Most important function is the ability to concentrate urine
- This is the segment responsible for ‘countercurrent multiplication’ (See Costanzo pg 288); NaCl is deposited in the interstitial fluid of the medulla and papillary areas, making them hyperosmolar
- The loop of Henle is composed of three parts:


The descending thin loop of Henle

- Highly permeable to H20 and small solutes
- Tubular fluid becomes progressively hyperosmolar as it moves toward the inner renal medulla (inner renal medulla is very hyperosmolar- 1200mOsm/L. This is primarily accomplished by removing water from the tubules by osmosis which decreases filtrate volume and increases solute concentration in the filtrate


Thin ascending loop of Henle

- Impermeable to H20
- Permeable to NaCl


Thick ascending limb of the Loop of Henle

- Impermeable to water
- Large amounts of Na+, Cl-, and K+ are actively transported from the tubules lumen making urine hypotonic, and the EFC hyperosmolar
- Site of action of “Loop Diuretics”(Furosemide –Lasix; ethacrynic acid); they impair Na+ CL- K+ pump by binding with the CL- site on the pump


Early portion of distal renal tubule

- Juxtaglomerular complex is located here. The JG complex is part of the feedback control of GFR
- Impermeable to H20
- Avidly reabsorbs ions –acts as ‘the diluting segment’


Late distal renal tubule and cortical collecting tubules

- the area of final processing of glomerular filtrate.
- Permeability to H20 is controlled by ADH (antidiuretic hormone)
- H+ is secreted into the lumen by intercalated cells
- ‘Principle cells’ absorb Na+ and H20 and secrete K+. Aldosterone acts here to increase Na+ absorption (trades K+ for Na+)


Medullary Collecting Ducts

- Final processing of urine
- H20 permeability controlled by ADH
- Secretes H+ against a large gradient


Hormones that Act on the Kidney

Renin is produce by the kidney; other hormones act on the kidney



- Produced and stored by the adrenal gland under direction from the pituitary gland
- Release of aldosterone is controlled by the renin-angiotensin-aldosterone system


Angiotensin II

- Stimulates aldosterone secretion which increases Na+ reabsorption late distal tubules and collecting ducts
- Directly stimulates Na+ reabsorption from proximal tubules
- Constricts efferent arterioles – increased reabsorbtive forces for Na+ and H20 at peritubular capillaries
- Secretion results in vasoconstriction of systemic vascular beds (a potential cause of chronic systemic hypertension)


. ADH (antidiuretic hormone; aka. vasopressin)

- ADH is a hormone of posterior pituitary
- The hypothalamus senses osmolarity of body fluids. If increased osmolarity is sensed, ADH is secreted from the pituitary resulting in increased reabsorption of H20 by the kidney producing concentrated urine. If serum /ECF osmolarity is low, ADH is withheld by the pituitary and the kidney removes water producing dilute urine
Pathophysiology: Diabetes insipidus; SIADH – syndrome of inappropriate ADH secretion


Atrial Natriuretic Peptide

- Secreted by cardiac atrial cells if there is distention of atria (too much preload)
- Inhibits reabsorption of Na+, H20 (opposed the action of aldosterone)


Parathyroid Hormone

- Secreted by the parathyroid gland in response to low serum Ca++
- Increases renal Ca++ reabsorption
-Decreases renal phosphate reabsorption


The Renal Role in Acid Base Homeostasis

The “slow mechanism” of regulation of acid-base dynamics

- Mechanisms:
o Synthesis and reabsorption from the tubules of HCO3-
o Excretion of fixed acids as NH4+


Pathophysiology: Renal Failure

“Uremia” and “Azotemia” are terms reflecting the buildup of nitrogen based waste products in the body as a consequence of inadequate renal function


Acute Renal Failure

Characterized by a rapid decline in renal function (hours to days)
- Primarily a result of a decline in GFR - Oliguria (Urine Output less than 400ml/day) is a common manifestation
- Patients are often able to regain renal function when underlying cause is corrected


Acute Renal Failure: Renal hypoperfusion

“Prerenal azotemia”, - hypovolemia - ex. inadequate replacement of circulation blood volume resulting in low cardiac output following events such as hemorrhage, GI fluid loss, or pancreatitis (third spacing); etc.


Acute Renal Failure: Intrinsic Acute Renal Failure

- Renovascular obstruction: ex. blood clots/atherosclerosis in the renal artery, aortic aneurisms obstructing renal artery
- Glomerular diseases and acute tubular necrosis (ATN);
ex. hemolysis; myoglobinuria, toxins, hypotension
- Interstitial nephritis such as post streptococcus glomerulonephritis, lupus nephritis


Acute Renal Failure: Post renal failure (obstruction)

- Ureteral obstruction ex. calculi, tumor
- Bladder outlet obstruction – ex. prostatic hypertrophy, tumor


Chronic Renal Failure (CRF)

- Characterized by a decline in GFR occurring over months to years
- Typically not reversible
- It reflects the severe loss of nephron mass
- Often progressive even with of successful treatment of underlying disease. ex. HTN, DM, obstruction, infection, etc.
- Anuria or absence of urine flow at end stage disease


Chronic Renal Failure (CRF)

Signs/ symptoms /medical problems associated with CRF: (think of the functions of the kidney)
- Uremia (the buildup of nitrogenous wastes)
- Hyperkalemia
- Metabolic acidosis
- Anemia
- Osteoporosis: abnormal calcium, phosphorus regulation - - Volume overload -CHF
- Peripheral neuropathy
- Anorexia
- Endocrine disturbances


The Urinalysis

Specific Gravity – S.G. range roughly from 1035 (extremely concentrated urine) to 1001 (extremely dilute urine). A SG of 1010 is approximately isotonic with normal serum osmolarity (295 mOsm/l)
-pH ranges 5-9; highly diet dependent


The Urinalysis

Abnormal constituents:
A. Glucose
B. Proteinuria
C. Hematuria (RBC’s or hemoglobin)
D. Presence of WBC,
E. Large numbers of crystals
F. Casts (“casts” are substances formed into the shape of the renal tubules as if they had been poured into a mold)
G. Bilirubin


Renal Function Serum (blood) Tests

1. Creatinine
2. BUN (blood urea nitrogen)
3. Creatinine Clearance


Prevention: Acute Renal Failure

- Maintenance of adequate hydration and circulating blood volume
- Great care when using potentially nephrotoxic drugs
- Adequate treatment of streptococcal infections
- If ARF occurs, support the patient until renal function recovers


Prevention: Chronic Renal Failure

- Aggressive treatment diabetes
- Optimum control (treatment) of hypertension,
- Adequate treatment of streptococcal infections
- Recognize early signs of renal compromise and refer/treat