LECTURE 7

Case Study 1: Mr P

- 45 years old

- Shortness of breath when climbing stairs

- Feeling tired despite no changes in routine

- Sallow complexion with a yellow tinge

- Pruritus (itching) especially at night

- Swollen ankles (peripheral edema)

- Peripheral neuropathy with tingling in fingers and toes

- Joint pain in ankles, shoulders, and hips

- Elevated blood pressure of 150/90 mmHg

What do the kidneys do:

- Without kidneys, we'd just be a bag of salty water, but you can survive with replacement treatments.

Anatomy of the Urinary System:

- The vena cava inferior is mentioned, along with the dimensions of the kidney located posterior to the abdominal wall.

- Adrenal glands are located on top, and there's a hilum where the artery enters and the vein leaves, similar to the respiratory system.

- The ureters connect the kidneys to the bladder and are specialized tubes of smooth muscle that undergo peristalsis.

- Peristalsis helps in bladder filling, even during the night when gravity assists in the process.

- The urethra is the way urine is excreted, longer in men and has a dual function with the reproductive system, while in females, it's shorter.

How do we Monitor the Urinary System:

- Monitoring the urinary system can be challenging due to its internal nature. Urine samples are helpful in determining what the system is producing.

- An intravenous pyelogram, using contrast medium, helps visualize the structures in the urinary system. It involves injecting a radio-opaque compound into the patient, which travels through the bloodstream to the kidneys for clear imaging. This method is non-invasive and provides valuable information about the urinary system.

Anatomy of the Kidney:

- The left kidney is slightly higher than the right one, with clear visibility of the ureters, vertebral column, pelvis, bladder, and attachments.

- This imaging is beneficial for detecting solid masses or blockages in the urinary system, such as tumors or kidney stones.

- When discussing the anatomy of the kidneys, the kidney's bean shape is highlighted, sparking a light-hearted debate on whether the kidney or kidney beans came first.

- The outer cortex, inner medulla, renal pelvis, major and minor calyces, and renal medulla are essential structures to understand.

Kidney Functional Unit: The Nephron

- The kidney has numerous nephrons, which are the functional units where all the action takes place. It starts with a knot of capillaries leading to the Bowman's capsule.

- Next comes the proximal convoluted tubule, which is close to the beginning, convoluted due to its shape, and leads to the loop of Henle with descending and ascending limbs.

- Following that is the distal convoluted tubule, located further down the nephron, which eventually drains into the collecting duct, leading to the minor and major calyces.

- There are over a million nephrons per kidney, and survival is possible with around 50% of them. The nephron structure is highly vascular.

Nephron Structure:

- Two main types of nephrons: cortical nephrons located in the cortex with the loop of Henle extending into the medulla, making up about 85% of nephrons.

- The other type is juxtamedullary nephrons found lower down, with the loop of Henle extending to the inner medulla, accounting for approximately 15% of nephrons.

Learning Outcomes:

- Nephron's unique vascularity with capillary beds in series, distinct from other body parts.

- Emphasis on the glomerulus, a cluster of capillaries, and branching into arterioles.

- Discussion on the intricate vascular network within the nephron.

Glomerular Filtration:

• Knot of capillaries surrounded by the Bowman's capsule.

• Blood comes in through the afferent arteriole and leaves through the efferent arteriole.

  Remember, afferent brings blood in, efferent is the exit. In the glomerulus, there's glomerular filtration happening, filtering protein-free plasma.

• This process allows some substances to move into the proximal convoluted tubule while keeping the proteins in the bloodstream.

• The filtration occurs through structures like the glomerular capillary wall, basement membrane, and the podocytes in the Bowman's capsule.

• It's all about that filtration process in the nephron.

Filtration Forces:

- Filtration forces help move components across.

- Hydrostatic pressure is the pressure in blood vessels, usually around 60 mmHg.

- Colloid osmotic pressure pulls fluids back due to proteins in the plasma.

- Capsular pressure is another negative pressure that contributes to pulling back fluids.

- Overall, there is a positive pressure of 10 mmHg moving across from the glomerulus.

- Maintaining pressure in the glomerulus is crucial for filtration; if it drops, kidneys can fail.

- Kidneys have a sophisticated system to ensure pressure is maintained, even in challenging situations.

Glomerular Filtration Rate:

So good Mariner filtration rate. It's good to be able to put a number on this so

we can monitor how people's nephrons are working. So going to run a filtration rate

is the volume of plasma per unit time the minutes whatever that is filtered by the

glomerulus and this is really good because we can monitor them if somebody's renal

function is changing.

How can we Measure Glomerular Filtration Rate:

- To measure renal function, we need a compound that can freely pass through the glomerulus into Bowman's capsule without being reabsorbed immediately back into the bloodstream.

- We should avoid compounds that can be affected by negative factors, reabsorbed into the bloodstream, excreted directly into the tubules, produced by the kidney, or metabolized.

- It's essential to find a compound that is easy to monitor and isn't impacted by these processes or doesn't alter the glomerular filtration rate.

What is used to measure GFR:

- Creatinine is a common measure of muscle mass and renal function as it's a product of skeletal muscle breakdown and proportional to muscle mass.

- Creatinine levels can be influenced by factors like bodybuilding, supplements, age, and muscle mass.

- Cystatin C is another marker used for estimating kidney filtration rates, especially in unwell or frail individuals.

- Inulin, not insulin, is an experimental compound that can be used to monitor movement through the urinary system → Often used as a negative clearance indicator.

When inulin is referred to as a negative clearance indicator, it means that the substance is not naturally produced or metabolized by the body. Instead, it is a compound that is introduced externally for the purpose of measuring kidney function. Inulin is used as a marker because it is not reabsorbed or secreted by the renal tubules, allowing for a more accurate determination of glomerular filtration rate.

Why is GFR Important:

- Glomerular filtration rate (GFR) is important because if it falls, it indicates potential damage to the renal system and the presence of disease.

- Blood pressure and the renal system are closely linked, which is of interest to you as a physiologist.

BP + GFR:

- Glomerular filtration rate (GFR) relies on maintaining blood pressure at about 10 mm of mercury in the glomerulus for proper filtration.

- Kidneys have mechanisms to adapt to changes in blood pressure to ensure they continue functioning properly.

- The kidneys can regulate blood flow and pressure by adjusting the diameter of the afferent and efferent arterioles within the glomerulus.

- Dilating the afferent arteriole and constricting the efferent arteriole increases the glomerular filtration rate (GFR) by allowing more blood in and raising the pressure.

- Constricting the afferent arteriole decreases GFR by reducing blood flow, while dilating the efferent arteriole increases GFR by letting more blood out and raising the pressure.

Autoregulation:

- Less blood flow through the afferent arteriole leads to reduced renal blood pressure.

- With less blood flow, the efferent arterioles relax slightly, leading to increased renal blood flow and a slight increase in GFR.

- Conversely, an increase in systemic blood pressure results in higher renal blood flow through the afferent arteriole, causing the arterioles to stretch and recoil slightly, leading to a decrease in blood flow and GFR.

Hormonal regulation:

The juxtaglomerular apparatus is an important part of the nephron located close to the Bowman's capsule and the glomerulus.

- Specialized juxtaglomerular cells can secrete the enzyme renin in response to a fall in renal blood flow.

- Renin converts angiotensinogen to Angiotensin 1, which is a key step in the renin-angiotensin-aldosterone system.

Autonomic Regulation:

- Sympathetic nervous system stimulation in extreme fight-or-flight situations can lead to powerful vasoconstriction of the afferent arterioles to regulate blood pressure.

- This vasoconstriction helps limit blood flow to prevent rapid changes in glomerular filtration rate (GFR) and conserve water by reducing the amount of substances being filtered, ultimately helping to limit fluid loss in stressful situations.

What Factors cause renal Blood Pressure to fall:

• When your blood volume drops suddenly, like in a traumatic incident or severe dehydration, it can cause your blood pressure to fall, leading to hypovolemic shock.

• This drop in blood pressure can affect your kidney function and alter your glomerular

  filtration rate (GFR). The body works to regulate these changes through various mechanisms.

• It's essential to address the underlying causes of hypovolemic shock to prevent further complications.

What was Wrong with Mr P:

- Mr. P had symptoms of haematuria (blood in urine) and proteinuria (protein in urine), indicating an issue with glomerular filtration.

- Causes of these symptoms can include renal failure, damage to the filtration apparatus (e.g., physical injury, chronic inflammation, bacterial infections), and mercury poisoning (which can poke holes in cell membranes).