Renal Physiology Lecture 1 — Functions of the Kidney & Nephron Processes
This lecture sets up the renal module by establishing two things: what the kidney does (its four functional roles) and how the nephron does it (the three basic processes and the mechanics of filtration). The clinical anchor is a case of chronic renal failure, which is used to show what fails when each kidney function is lost. The back half moves from gross nephron structure down to the glomerular filtration barrier, the Starling forces driving filtration, and the quantitative concepts (GFR, clearance) used to measure renal function.
The four functions of the kidney
The lecture organises everything under four headings. Be able to name all four and give examples of each.
- Excretion: removal of water, salts, metabolic wastes, and foreign substances.
- Homeostasis: acid-base balance, fluid balance, electrolyte balance.
- Hormones: the kidney as an endocrine organ (erythropoietin, calcitriol, and others).
- Metabolism: gluconeogenesis and ammonia synthesis.
Understand the conceptual point captured by the Homer Smith quote: blood composition is set by what the kidney retains, not by what is ingested. The kidney’s role is regulatory, not just disposal.
Function 1: Excretion
- Know what gets excreted, grouped into three categories:
- Surplus water and electrolytes, excreted to maintain homeostatic balance (especially ECF volume and composition).
- Metabolic waste products: nitrogenous wastes (urea, uric acid), hormones, bile pigments.
- Foreign substances: toxins, drugs.
Function 2: Homeostasis
- Acid-base: synthesis of HCO3 and excretion of non-volatile acids.
- Fluid balance: urine output is adjusted to maintain both volume and osmolarity.
- Electrolyte balance: renal control of Na, K, Ca, PO4. Understand the principle that most electrolytes are kept in balance by what is excreted rather than by controlling what is absorbed.
Function 3: Hormones
- Know the list of renal hormones: erythropoietin, calcitriol, renin, dopamine, kallikrein, prostaglandins.
- Erythropoietin: the kidney detects low oxygen, releases erythropoietin, which stimulates bone marrow to produce more red cells. Clinical link: chronic renal failure causes anaemia.
- Vitamin D / calcitriol: vitamin D is essential for calcium balance and bone mineralisation. It requires conversion to its active form, calcitriol. The renal enzyme 1-hydroxylase catalyses the final conversion step. Clinical link: chronic renal failure causes calcium and bone problems (renal osteodystrophy).
Function 4: Metabolism
- Gluconeogenesis: synthesis of glucose from amino acid precursors occurs in the kidney (as well as the liver).
- Ammonia (NH3): synthesised and secreted by the kidney; has a role in both nitrogen balance and pH balance.
Clinical correlate: chronic renal failure
Be able to map the case findings back onto the four functions, since the whole case is a demonstration of what fails. The 58-year-old presents with lethargy, nausea, poor appetite, nocturia, swollen ankles, shortness of breath, and 6 kg weight gain, with elevated JVP, crackles, and hypertension (150/100).
- Fluid overload (weight gain, oedema, elevated JVP, SOB, crackles, hypertension): loss of fluid and electrolyte excretion.
- Raised urea (49) and creatinine (0.794), GFR 2.2 ml/min: loss of excretion of nitrogenous waste and collapse of filtration.
- K 5.6 (high): loss of electrolyte balance.
- Hb 90 (low): loss of erythropoietin.
- pH 7.32, HCO3 16, PaCO2 32: metabolic acidosis (loss of HCO3 synthesis and acid excretion), with a compensatory drop in PaCO2.
Nephron structure
- The nephron is the functional unit. Know there are roughly one million (10⁶) per kidney.
- Know the components: glomerulus and tubules, afferent and efferent arterioles, peritubular capillaries and vasa recta.
- Know the two populations: about 80% cortical and about 20% juxtamedullary (the latter have long loops reaching into the medulla).
- Understand the structural layout shown in the nephron diagrams: the renal corpuscle (glomerulus plus glomerular capsule) sits in the cortex; the proximal tubule, loop of Henle (thin descending limb, thick ascending limb), distal tubule, and collecting duct trace a path from cortex into the medulla. Associated vasculature includes interlobular and arcuate arteries/veins and the vasa recta.
The three nephron processes
- Know the three basic processes and what each does:
- Filtration: creates a plasma-like filtrate of the blood (at the glomerulus).
- Reabsorption: removes useful solutes from the filtrate and returns them to the blood.
- Secretion: adds further wastes from the blood into the filtrate, sourced from the tubule rather than from filtration.
- Understand the net excretion relationship: amount excreted = amount filtered − amount reabsorbed + amount secreted. The balance of the three processes determines how any given substance is handled.
- Know which process dominates in which segment:
- Glomerulus: filtration.
- Proximal tubule: bulk reabsorption.
- Distal tubule: fine-tuning of electrolytes and pH.
- Collecting duct: fine-tuning of water reabsorption.
Filtration: scale and selectivity
- Understand that glomerular filtration is not particularly selective.
- Know the numbers: about 180 litres filtered per day, but only about 1.5 litres of urine produced. This is why reabsorption matters, captured by the phrase “all out, useful stuff back, waste left behind.”
The glomerulus and juxtaglomerular apparatus
- Know the glomerular components: afferent and efferent arterioles; a fenestrated capillary tuft; podocytes lining Bowman’s capsule (the blind end of the tubule into which the glomerulus protrudes); mesangial cells and matrix providing support.
- Understand the juxtaglomerular apparatus (JGA): the interface where the distal tubule meets the glomerulus, made up of the macula densa (distal tubule cells) and granular cells (in the arteriole wall).
Glomerular filtration as ultrafiltration
- Understand that glomerular filtration is a specialised form of ultrafiltration, with roughly 100 times the permeability of normal capillaries.
- Know what is filtered versus retained: filtered = plasma water and small solutes; retained = blood cells and proteins.
- Know the path: from the lumen of the glomerular capillary, via the filtration barrier, to Bowman’s capsule.
- Note the molecular weight figures given for the cutoff (slides state ~100,000 / 70,000, with negatively charged molecules restricted).
The glomerular filtration barrier (three layers)
Know the three layers in order and what each contributes:
- Fenestrations of the endothelial cells (glomerular capillary): act as a size barrier (slide states “70 daltons”).
- Basement membrane (shared by capillary and podocytes): carries a negative charge, which repels proteins.
- Filtration slits of the podocytes (between foot processes): size-selective, formed by a diaphragm containing nephrins.
Forces driving filtration
- Understand that GFR is determined by: the pressure gradient between the glomerular capillary and Bowman’s space, the permeability of the glomerular capillary, and its surface area. The permeability and surface area are combined in Kf, the ultrafiltration coefficient (about 100x greater than systemic capillaries).
- Know the net filtration pressure equation and the typical values:
- Net filtration pressure = glomerular hydrostatic pressure − Bowman’s capsule pressure − glomerular oncotic pressure.
- Glomerular hydrostatic pressure 60 mmHg, Bowman’s capsule pressure 18 mmHg, glomerular oncotic pressure 32 mmHg, giving a net of 10 mmHg.
- Understand the renal vessel pressure profile: pressure stays high through the arteries, drops across the afferent arteriole to about 60 mmHg in the glomerular capillaries, then drops sharply across the efferent arteriole to a low value in the peritubular capillaries. The efferent arteriole is the key resistance point that sustains glomerular pressure.
GFR: definition and figures
- Know the definition: the amount of fluid filtered across the glomerulus per unit time.
- Know the typical value: about 180 L/day or 125 ml/min.
- Know the qualifiers: it is tightly regulated by intrinsic and extrinsic mechanisms, varies between people, is normalised as about 70 ml/min/m² body surface area (1.73 m²), and declines slowly from age 30.
- Know single-nephron GFR (SNGFR): about 60 nl/min.
Renal flow and clearance concepts
- Know renal plasma flow (RPF) = RBF × (1 − Hct), estimated using PAH.
- Know filtration fraction = GFR / RPF, about 20%.
- Know filtered load = amount of solute filtered per minute = GFR × plasma concentration of the solute.
- Know clearance = UV/P, where P is plasma concentration, U is urine concentration, and V is urine production rate (ml/min). Understand that clearance indicates how a substance is handled by the kidney and can be calculated for any substance.
Using clearance to estimate GFR
Understand the logic chain:
- If a substance is filtered but neither reabsorbed nor secreted, then the amount filtered equals the amount appearing in urine.
- Therefore GFR × P = U × V, which rearranges to GFR = UV/P = clearance.
- Creatinine approximates such a substance, so creatinine clearance is used to estimate GFR. Inulin is more accurate but must be injected.
Self-test checklist
- Can you name the four functions of the kidney and give an example of each?
- Can you explain the renal role of erythropoietin and what its loss causes?
- Can you explain why renal failure causes bone disease, naming the enzyme involved?
- Can you list what is excreted under each of the three excretion categories?
- Can you map each abnormal value in the chronic renal failure case to a lost kidney function?
- Can you state the three nephron processes and write the net excretion equation?
- Can you say which process dominates in each nephron segment?
- Can you explain why 180 L is filtered but only 1.5 L of urine is produced?
- Can you name the three layers of the filtration barrier and the selectivity each provides?
- Can you write the net filtration pressure equation and recall the four pressure values?
- Can you explain why pressure drops sharply across the efferent arteriole and why that matters?
- Can you state the normal GFR and how it is normalised to body surface area?
- Can you define clearance, filtration fraction, and filtered load?
- Can you derive GFR = UV/P and explain why creatinine is used to estimate it?