Final Exam L20

Anatomy and Roles of the Kidney

Gross anatomy

The kidney’s gross anatomy includes the outer renal cortex, inner renal medulla, blood supply via renal artery/vein, and the ureter linking kidney to bladder.

Anatomy and Roles of the Kidney

Kidney is highly vascular

The kidneys get ~25% of cardiac output; most blood flows through the cortex with low O₂ use, while the medulla gets less blood but uses ~80% of its O₂, making it vulnerable to hypoxia.

Anatomy and Roles of the Kidney

The nephron

Each kidney has 1–2 million nephrons (functional unit), where glomeruli in Bowman’s capsule filter blood; filtrate then passes through tubules for reabsorption/secretion, forming urine that drains to the bladder via the ureter.

Anatomy and Roles of the Kidney

Roles of the kidneys

The kidneys filter blood to excrete waste, regulate pH, electrolytes, and water, perform gluconeogenesis (important in starvation), and have endocrine roles: releasing erythropoietin, renin, and activating vitamin D.

Function of the Kidney

Urine Production

Synthesis of urine involves filtration, reabsorption and secretion

Filtration – what is filtered

About 20% of plasma is filtered at the glomeruli (~60×/day), producing ultrafiltrate with water, glucose, salts, urea, and amino acids, but not cells or large proteins; kidney dysfunction is indicated by albumin in urine or high serum creatinine (used to estimate GFR).

glomerular function by blood test

Reabsorption and secretion occur in the tubule

Most filtrate is reabsorbed in the tubules (e.g., ~99% water, Na⁺, glucose, HCO₃⁻), while secretion moves solutes into urine; failure to clear wastes causes azotemia/uremia, and exceeding transport limits (e.g., glucose >220 mg/dL in diabetes) leads to solute loss in urine.

azotemia in asymptomatic patients or uremia when symptoms such as nausea and vomiting are present

Levels of urea and creatinine in the blood are important indicators of renal function. When these
waste products accumulate in a patient’s serum it is called azotemia in asymptomatic
patients or uremia when symptoms such as nausea and vomiting are present.

Renal threshold

For most substances that are actively reabsorbed or secreted there is a limit to the rate at which the solute can be transported. For example, when the filtered load of a solute exceeds the capacity of the tubules to reabsorb that solute, urinary excretion of that substance occurs.

Tubular secretion

The kidneys secrete endogenous wastes (uric acid, creatinine) and many drugs, with urine composition determined by excretion = filtration – reabsorption + secretion.

Acid-Base Homeostasis
Renal regulation of pH is mediated by differential absorption and secretion.

The kidneys regulate pH by reabsorbing bicarbonate, secreting H⁺, and metabolizing glutamine to produce 2 molecules of ammonia (NH₄⁺) for excretion, adjusting transporter activity as needed.

Fuel Metabolism of the Kidney

The kidney is metabolically very active

Aerobic versus anaerobic metabolism

The kidneys use ~10% of the body’s O₂ for mostly aerobic metabolism to support ATP-dependent reabsorption, while medullary regions rely partly on anaerobic metabolism, using fuels like glucose, lactate, citrate, fatty acids, ketone bodies, and amino acids.

Gluconeogenesis

The kidney performs gluconeogenesis (mainly in the cortex), producing 20–50% of liver glucose, crucial during starvation or acidosis to maintain blood glucose.

Endocrine Function of the Kidney

Erythropoietin

Erythropoietin, produced by the kidneys in response to low oxygen, stimulates bone marrow to make red blood cells, and its deficiency in kidney disease can cause anemia.

Renin

Renin (in response to granular cells), secreted by the kidney when blood pressure drops, cleaves angiotensinogen to angiotensin I, which ACE converts to angiotensin II, causing vasoconstriction and aldosterone-mediated Na⁺/water retention; renin is rate-limiting and regulated by feedback, and this pathway is targeted in hypertension treatments.

Clinical Aspects of the Kidney

Monitoring kidney function

Kidney failure causes high blood pressure, back pain, abnormal red/rusty brown colored urine, and edema due to protein (albumin) loss lowering oncotic pressure; serum BUN, creatinine, uric acid rise, GFR falls, urine shows protein/cells, and endocrine issues include anemia (low erythropoietin) and blood pressure problems (low renin).

Anuria

Oliguria

Polyuria

Anuria: no urine

oliguria: minimal urine production

polyuria: excessive

Causes of changes to kidney function

Acute renal failure

Acute renal failure: rapid and frequently reversible deterioration of renal function

• Pre-renal causes:
• Renal causes:

Rhabdomyolysis:

• Post-renal causes:

• Pre-renal causes: loss of blood volume, hemorrhage, congestive heart failure
• Renal causes: infections, toxins and rhabdomyolysis
Rhabdomyolysis: damage to skeletal muscle results in release of myoglobin which
appears in the blood and urine, causing a brown discoloration of urine. Myoglobin is
extremely toxic to the kidneys. Rhabdomyolysis can be caused by excessive exertion, heat or crushing injuries to skeletal muscle.
• Post-renal causes: cancer, obstruction of the ureter or urethra (e.g., kidney stone)

Chronic renal failure:

Chronic renal failure: slower,
progressive irreversible loss of renal
function. This can result from a variety
of diseases, but complications from
diabetes cause approximately 40% of all
cases in the US; hypertension causes
~20%.

There are 5 stages of kidney failure ranging from slight damage to failure requiring dialysis or transplant. GFR decreases as damage increases.

Pancreas

Pancreatic anatomy

The pancreas has a head near the duodenum; its exocrine acinar cells release digestive enzymes into ducts, while the endocrine Islets of Langerhans secrete hormones like insulin and glucagon.

Functions of the pancreas

Endocrine vs exocrine functions

Endocrine functions: Islets of Langerhans (only about 1-2% of the pancreas), connected
to blood vessels that allow for secretion of hormones into blood.
• Insulin secreted from β-cells in response to high blood glucose
• Glucagon secreted from α-cells in response to low blood glucose

Exocrine functions: acinar cells secrete pancreatic digestive enzymes and pancreatic ductal cells secrete bicarbonate important for digestion of food.

zymogens (inactive enzymes)

Enzymes are usually secreted as zymogens (inactive enzymes) and are activated in the
small intestine. This helps to prevent auto-digestion of the pancreas.

Markers of pancreatic damage

Pancreatic damage releases digestive enzymes into the blood, mainly amylase and lipase, serving as markers of injury.

Pancreatitis

Pancreatitis is inflammation of the exocrine pancreas, causing pain, tissue damage, and potential loss of function, often from premature activation of digestive enzymes inside the pancreas. Auto-activation of pancreatic digestive enzymes

Pancreatitis symptoms

Symptoms
• Abdominal pain that may radiate to the back, chest and sides
• Nausea and vomiting
• Low-grade fever
• Tachycardia (elevated heart rate)
• Hypotension
• Decreased pancreatic digestive enzymes (EPI, lecture 13) leading to undigested food
contents remaining in GI tract and causing complications such as steatorrhea

Pancreas diagnosis

Diagnosis
• Physical symptoms + increased amylase and lipase in blood
• White blood cells are also often elevated
NOTE: In severe chronic pancreatitis the enzymes may not be elevated because the
pancreas can no longer make them!

Pancreas causes/treatment

Chronic/excess alcohol consumption

Gallstones/blockage of ducts - This can lead to
auto-activation of enzymes and self-digestion of the pancreas.

Treatment: analgesics, IV fluids and nutrition