Case 1

An 18-year old female was recently admitted for hypokalemia. Part of the work up done were tests to check the function of her kidney. Confused, she asks
her doctor about it, claiming that she has not noticed any change in her urine. She wonders if her condition may be an effect of her dietary habits – she
doesn't consume fruits and prefers meals that are more protein based.

ANATOMY
1. Describe the kidneys, its location and position
2. Describe the formation of the renal excretory ducts (urine excretion/drainage)
3. Describe the relations at the hilum of the kidney

HISTOLOGY
1. Describe the nephron, its components, its major divisions and its role in filtration of the blood
2. Discuss the organization of the renal vascular system

PHYSIOLOGY
1. Discuss urine formation, concentration/dilution
2. Discuss the renal regulation of ions

BIOCHEMISTRY
1. Describe protein turnover, indicate the mean rate of protein turnover in healthy individuals, and provide examples of human proteins that are
degraded at rates greater than the mean rate
2. Amino acid catabolism is part of the larger process of the metabolism of nitrogen containing molecules. Nitrogen enters the body in a variety of
compounds present in food, the most important being amino acids contained in dietary protein. Nitrogen leaves the body as urea, ammonia, and
other products derived from amino aicd metabolism.
Describe two important process involved with body proteins: the amino acid pool and protein turnover
PRECEPTOR'S COPY

Case 1

An 18-year old female was recently admitted for hypokalemia. Part of the work up done were tests to check the function of her kidney. Confused,
she asks her doctor about it, claiming that she has not noticed any change in her urine. She wonders if her condition may be an effect of her
dietary habits – she doesn't consume fruits and prefers meals that are more protein based.

ANATOMY
1. Describe the kidneys, its location and position

The kidneys are two bean-shaped organs found in vertebrates. They lie retroperitoneally on the posterior abdominal wall, one on each side of the vertebral
column at the level of the T12–L3 vertebrae. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is
attached to a ureter, a tube that carries excreted urine to the bladder.
During life, the kidneys are reddish brown and measure approximately 10 cm in length, 5 cm in width, and 2.5 cm in thickness. Superiorly, the posterior
aspects of the kidneys are associated with the diaphragm, which separates them from the pleural cavities and the 12th pair of ribs.
More inferiorly, the posterior surfaces of the kidney are related to the psoas major muscles medially and quadratus lumborum muscle. The liver, duodenum,
and ascending colon are anterior to the right kidney. This kidney is separated from the liver by the hepatorenal recess.
The left kidney is related to the stomach, spleen, pancreas, jejunum, and descending colon.
Each kidney moves 2–3 cm in a vertical direction during the movement of the diaphragm that occurs with deep breathing. Because the usual surgical
approach to the kidneys is through the posterior abdominal wall, it is helpful to know that the inferior pole of the right kidney is approximately a finger’s
breadth superior to the iliac crest

2. Describe the formation of the renal excretory ducts (urine excretion/drainage)

The renal pelvis is the flattened, funnel-shaped expansion of the superior end of the ureter. The apex of the renal pelvis is continuous with the ureter. The
renal pelvis receives two or three major calices(calyces), each of which divides into two or three minor calices. Each minor calyx is indented by a renal
papilla, the apex of the renal pyramid, from which the urine is excreted. In living persons, the renal pelvis and its calices are usually collapsed (empty). The
pyramids and their associated cortex form the lobes of the kidney. The lobes are visible on the external surfaces of the kidneys in fetuses, and evidence of
the lobes may persist for some time after birth.

3. Describe the relations at the hilum of the kidney

At the hilum, the renal vein is anterior to the renal artery, which is anterior to the renal pelvis. Within the kidney, the renal sinus is occupied by the renal
pelvis, calices, vessels, and nerves, and a variable amount of fat. Each kidney has anterior and posterior surfaces, medial and lateral margins, and superior
and inferior poles.

HISTOLOGY
1. Describe the nephron, its components, its major divisions and functions

A nephron is the functional unit of the kidney. Each kidney contains 1-4 million units, each consisting of a corpuscle and a long, simple epithelial renal
tubule. The major divisions of each nephron are:
– Renal corpuscle – initial dilated part enclosing a tuft of capillary loops and the site of blood filtration, always located in the cortex
– Proximal tubule – has a long convoluted part (within the cortex), and a shorter, straighter part that enters the medulla
– Loop of Henle (in the medulla) – has a thin descending and a thin asceding limb
– Distal tubule – has a thick straight part that ascends from the Loop of Henle back into the cortex and a convoluted part (in the cortex)
– Connecting tubule – a short minor part linking the nephrons to collecting ducts
Functions of the urinary system:
Ion and acid-base balance
Excretion of metabolic wastes
Excretion of bioactive substances
Secretion of renin
Secretion of erythropoietin
Conversion of steroid prohormone vit D to active form calcitriol
Gluconeogenesis during starvation or periods of prolonged fasting

These functions involves filtration, tubular secretion and tubular reabsorption

Blood filtration – each renal corpuscle is about 200 micrometers in diameter and contains ad tuft of glomerular capillaries surrounded by a double walled
epithelial capsule (glomerular/Bowman's capsule). Filtration occurs through a structure with 3 parts – fenestrations of the capillary endothelium (blocks
blood cells and platelets), the thick combined basal laminae/GBM (restricts large proteins and some organic anions) and the filtration slit diaphrams
between pedicels (restricts some small proteins and organic anions)

2. Discuss the organization of the renal vascular system

Renal artery divides into segmental arteries at the hilum

Around the renal pelvis, the segmental arteries branch into the interlobar arteries that extend between the renal pyramids towards the corticomedullary
junction
At the junction, the interlobar arteries divide into the arcuate arteris that run along the base of each renal pyramid
These radiate into the arcuate arteries that extends deeply into the cortex

From these arises the microvascular afferent arterioles that divide to form the glomerulus (a plexus of capillary loops) that drain into the efferent arterioles.
These branch into the peritubular capillaries (in the cortex) or the vasa recta (from the juxtaglomerular corpuscles near the medulla)

Capillaries converge into small stellate veins that empty into the interlobular veins.

Blood leaves the kidneys in veins that follow the same courses as arteries and have the same names.

PHYSIOLOGY
1. Discuss urine formation, concentration/dilution
2. Discuss the renal regulation of ions

BIOCHEMISTRY
1. Describe protein turnover, indicate the mean rate of protein turnover in healthy individuals, and provide examples of human proteins
that are degraded at rates greater than the mean rate

The continuous degradation and synthesis (turnover) of cellular proteins occur in all forms of life. Each day, humans turn over 1% to 2% of their total body
protein, principally muscle protein. High rates of protein degradation occur in tissues that are undergoing structural rearrangement, for example, uterine
tissue during pregnancy, skeletal muscle in staand tadpole tail tissue during metamorphosis. While approximately 75% of the amino acids liberated by
protein degradation are reutilized, the remaining excess free amino acids are not stored for future use. Amino acids not immediately incorporated into new
protein are rapidly degraded. The major portion of the carbon skeletons of the amino acids is converted to amphibolic intermediates, while in humans the
amino nitrogen is converted to urea and excreted in the urine.

2. Amino acid catabolism is part of the larger process of the metabolism of nitrogen containing molecules. Nitrogen enters the body in a
variety of compounds present in food, the most important being amino acids contained in dietary protein. Nitrogen leaves the body as
urea, ammonia, and other products derived from amino aicd metabolism.
Describe two important process involved with body proteins: the amino acid pool and protein turnover

ANSWER:
A. Amino acid pool
Amino Acids: Disposal of Nitrogen Free amino acids are present throughout the body,
for example, in cells, blood, and the extracellular fluids.
For the purpose of this discussion, envision all these amino acids as if they belonged to a
single entity, called the amino acid pool
. This pool is supplied by three sources: 1) amino acids provided by the degradation of
body proteins, 2) amino acids derived from dietary protein, and 3) synthesis of
nonessential amino acids from simple intermediates of metabolism
Conversely, the amino pool is depleted by three routes: 1) synthesis of body protein,
2) amino acids consumed as precursors of essential nitrogen-containing small
molecules, and 3) conversion of amino acids to glucose, glycogen, diets); 100 g/day is
typical of the U.S. diet.
Body protein Synthesis of non Synthesis of nonessential amino acids essenti ami no al
~400 g/day Amino acid pool aci ds Var Varies ies ~30 g ~30 g/day /day Body protein

~400 g/day Varies Glucose, glycogen Synthesis of: • Porphyrins • Creatine •

Neurotransmitters • Purines • Pyrimidines • Other nitrogen containing compounds
Ketone bodies, fatty acids, steroids 2 2O O The amino acids not used in biosynthetic
reactions are burned as a fuel. Figure 19.2 Sources and fates of amino acids. fatty acids,
ketone bodies, or CO2 + H2O (Figure 19.2). Although the amino acid pool is small
(comprised of about 90–100 g of amino acids) in comparison with the amount of protein
in the body (about 12 kg in a 70-kg man), it is conceptually at the center of whole-body
nitrogen metabolism.

B. Protein turnover
Most proteins in the body are constantly being synthesized and then degraded,
permitting the removal of abnormal or unneeded proteins. For many proteins,
regulation of synthesis determines the concentration of protein in the cell, with protein
degradation assuming a minor role. For other proteins, the rate of synthesis is
constitutive, that is, relatively constant, and cellular levels of the protein are controlled
by selective degradation.
Rate of turnover:
In healthy adults, the total amount of protein in the body remains constant, because the
rate of protein synthesis is just sufficient to replace the protein that is degraded. This
process, called protein turnover, leads to the hydrolysis and resynthesis of 300–400 g of
body protein each day. The rate of protein turnover varies widely for individual
proteins. Short-lived proteins (for example, many regulatory proteins and misfolded
proteins) are rapidly degraded, having half-lives measured in minutes or hours. Long-
lived proteins, with half-lives of days to weeks, constitute the majority of proteins in the
cell. Structural proteins, such as collagen, are metabolically stable, and have half-lives
measured in months or years.

Protein degradation:
There are two major enzyme systems responsible for degrading damaged or unneeded
proteins: the ATP-dependent ubiquitin-proteasome system of the cytosol, and the ATP-
independent degradative enzyme system of the lysosomes. Proteasomes degrade
mainly endogenous proteins, that is, proteins that were synthesized within the cell.
Lysosomal enzymes) degrade primarily extracellular proteins, such as plasma proteins
that are taken into the cell by endocytosis, and cell-surface membrane proteins that are
used in receptor-mediated endocytosis.