What is the functional unit of the kidney and what are its constituent parts, in sequence?
Glomerulus > PCT > Loop of Henle > Distal Convoluted Tubule > Collecting Duct.
Lecture: Kidney Anatomy and Histology
Objective 2: Describe the components of the nephron (the basic functional unit of the kidney) and its histologic features.
Given a 70kg mass human, calculate volume of Total Body Water, Intracellular Fluid, Extracellular Fluid (Plasma and Interstitial Fluid) and indicate the predominate ions present in Intracellular Fluid and Extracellular Fluid (Water density = 1kg/L)
- Total Body Water: 42L (60% of Total Body Mass)
- Intracellular Fluid: 28L (40% of Total Body Mass)
- Predominant Ion: K+ (also Mg2+, organic phosphates like ATP)
- Extracellular Fluid: 14L (1/3 of Total Body Water OR 20% of Total Body Mass)
- Predominant Ions: Na+, Cl-, HCO3-
- Plasma: 3.5L (25% of ECF)
- Interstitial Fluid: 10.5L (75% of ECF)
Helpful Mnemonics (from First Aid):
- HIKIN: HI K Intracellularly
- 60-40-20 rule: Allows you to calculate TBW, ICF, and ECF based on Total Body Mass
- Total Body Water: 60% of Total Body Mass
- ICF: 40% of Total Body Mass
- ECF: 20% of Total Body Mass
Lecture: Body Fluid Compartments, Osmosis, and Basic Kidney Functions
Objective 1: Understand body fluid compartmentalization
How does fluid compartmentalization shift when a patient presents with non-secretory diarrhea and why?
Non-secretory diarrhea is a situation of Hypoosmotic Fluid Loss (most common clinical volume loss).
- Initial Effect:
- Decrease in volume
- Increase in osmolality* (this creates a driving force for water to move from the ICF)
- UNCHANGED in both volume and osmolality
- Final Effect (2 stages because ICF will respond to the increased ECF Osm)
- Increase in volume (though not enough to compensate for the loss – so net decrease in volume still applies)
- Decrease in osmolality until ICF Osm = ECF Osm (typically still resulting in a net increase in osmolality)
- Decrease in volume (as water moves from ICF to ECF)
- Increase in osmolality until ICF Osm = ECF Osm
Lecture: Body Fluid Compartments, Osmosis, and Basic Kidney Functions
Objective 4: Understand osmosis, osmolality, and responses of cells to changing osmotic environments.
What are the three primordia of the kidney?
Which becomes the permanent kidney and which contributes to the development of the male internal genitalia?
Pronephros, Mesonephros, and Metanephros. Permanent Kidney = Metanephros. Male Internal Genitalia = Mesonephros.
Lecture: Urinary System Development
Objective 2: Appreciate the development of the primitive kidney: the pronephros and mesonephros.
How do you distinguish Cortical and Juxtamedullary Nephrons and what is the functional difference between the two?
Cortical and Juxtamedullary Nephrons are distinguished based on the location of their glomeruli – with cortical nephrons having glomeruli located in the mid to outer cortex and juxtamedullary nephrons having glomeruli located in the boundary of the cortex and outer medulla. Functionally, cortical nephrons are responsible for 95% of filtration and juxtamedullary nephrons are responsible for countercurrent multiplication (aka urine concentration)
Lecture: Functional Renal Anatomy and Glomerular Filtration
Objective 1: Understand critical features of renal anatomy and histology as they relate to function
Describe what the relationship between Clearance and Glomerular Filtration Rate can tell you about a particular substance.
Clearance is the virtual volume of plasma from which the substance is completely cleared per unit time. It can be used in comparison with Glomerular Filtration Rate to determine whether a substance is net reabsorbed or secreted by the renal tubules. If x is the substance of interest…
- Cx < GFR: net tubular reabsorption and/or not freely filtered
- Cx = GFR: no net secretion or reabsorption
- Cx > GFR: net tubular secretion
Lecture: Regulation and Measurement of Glomerular Filtration
Objective: Understand the basic concept of Clearance
Fanconi syndrome presents as a generalized reabsorption defect in the Proximal Convoluted Tubule. Given this information, what are key substances you’d find in a urine sample of a patient with Fanconi Syndrome that you would not find in a normal urine sample?
Amino acids, glucose, HCO3-, K+, Phosphates. The proximal tubule is responsible for 100% of the reabsorption of glucose and amino acids, so presence of these substances in the urine is pretty big red flag that there’s a PCT defect.
Lecture: Functions of the Renal Tubules I
Objective 2: Describe the structure and function of the proximal tubule.
Describe how the Thin Descending Loop of Henle and the Thick Ascending Loop of Henle differ in their permeability to H20 and what effect this has on solute concentration in that segment?
The Thin Descending Loop of Henle is permeable to H20 while the Thick Ascending Loop of Henle is impermeable to H20. This allows solute to become more concentrated as urine descends and to become less concentrated as urine ascends.
Lecture: Functions of the Renal Tubules II
Objective 4: Understand the counter-current multiplier effect of the loop of Henle
Describe the distribution within the body compartments, what transporter is key in maintaining this distribution and why it is so tightly regulated?
98% of K+ is held within the ICF vs. 2% in the ECF. This is maintained by the action of the Na+-K+ ATPase, and maintenance of this gradient is critical because alterations in K+ ratios intracellular and extracellularly can have devastating effects on the function of heart and skeletal muscle (See Guiding Question 7 in LG for specific EKG effects).
Lecture: Potassium/Transport of Potassium at the Cellular and Kidney Level
Objective 1: Describe the distribution of K+ within the body compartments
What is the significance of finding casts in the urine and how are they formed?
In the context of hematuria/pyuria, casts indicate that the problem is glomerular or renal tubular in origin. This is because casts are formed as a result of damage to renal tubular cells; as the cellular debris aggregates, it takes on the shape of the tube around it.
Objective 3: Explain how urinary casts are formed and what diseases they may represent.
Why is the urine sodium or fractional excretion of sodium low in patients with pre-renal AKI?
The pathophysiology of Pre-Renal AKI involves some process that reduces renal perfusion, which ultimately decreases GFR. These include causes such as hypovolemia, decreased cardiac output, etc… When this happens, the body responds by activating the RAAS system, increasing aldosterone (which increases sodium reabsorption in the distal nephron) and ultimately reducing the amount of sodium excreted in the urine.
Lecture: Acute Kidney Injury: Pre, Post, and Intrinsic
Objective 4: Define acute kidney injury.
Describe the pathophysiology of Gitelman Syndrome – how is this related to _____ class of diuretics?
Gitelman syndrome is an inherited disorder that results in a loss of function mutation in the Na-Cl symporter found in the Distal Convoluted tubule. This same symporter is targeted by thiazide diuretics to induce natriuresis. Therefore, if you think of these patients as having an intrinsic thiazide diuretic mechanism, they would fall into the set of patients with inherited blood pressure regulation disorders that present with hypotension.
Lecture: Sodium Balance and Control of Extracellular Fluid Volume
Objective 3: Understand inherited disorders affecting blood pressure.
Potassium sparing diuretics such as Amiloride act in what cell type in what portion of the nephron?
What is their mechanism of action?
Amiloride blocks sodium channels (ENaC) on the luminal side of Principal Cells in the Cortical Collecting Duct. Blocking the entry of sodium into the cell 1) promotes natriuresis and 2) reduces the driving force for the excretion of K+.
Lecture: Water Balance and Urinary Concentration; Potassium Balance
Objective 4: Understand mechanisms of internal and external potassium balance.