Patho: Renal

• Function of the Kidneys (6 key functions) 

  • Filtration and removal of nitrogenous waste, and the elimination of drugs and metabolites
  • Regulation of blood pressure and body fluid composition
  • RAAS 
  • Maintain osmolarity 
  • Control levels of electrolytes and metabolites 
  • Regulate blood pH
  • With H and HCO3 regulaiton 
  • Production of erythropoietin (hormone) 
  • To make RBCs 
• Urinary system structure

  2 bean shaped kidneys, about the size of your fist --> Located under the 12th rib. 

  Right kidney is slightly lower than the left d/t the liver. 

  Each kidney has 1 blood supply from the renal artery 

  Each kidney has a ureter. 
• Kidneys are the site of urine formation. 

  Composed of an outer cortex and inner medulla. 

  Important: Urine leaving the nephron flows into the renal pelvis prior to passing through the ureter and into the bladder itself. 

  • Different nephrons connect to the renal pelvis.
• The nephron is the unit of the kidney. 

  Each renal artery supplies blood flow to the renal cortex. From there, the blood vessels get progressively smaller and bifurcate. Eventually become small afferent arterioles that feed the glomeruli.

  Within the medulla - the loop of Henle and collecting duct are found. (see picture - the dark blue is the medulla) 

  • There are a large number of capillaries that encircle the nephron (see picture below).
• In the glomerulus

  • The blood vessel ball (see pic)
  • Afferent arterioles - take the blood to the glomeruli 
  • Efferent arterioles take blood to systemic circulation
  • They form a complicated network of capillaries that wrap around basically every distribution point along the nephron to form a portal system* 
  • Important because reabsorption occurs from the nephron units themselves into the bloodstream.
• Process: 

  1. Blood flows into the glomerulus → gets filtrated
  2. Then throughout the rest of the structure, the filtered fluid (the one that passed through the glomerulus) will be selectively reabsorbed (things like water, nutrients, and other needed substances) back into the bloodstream. Waste products will remain in the nephron and be eliminated in the urine.
• *Portal system: it is a special circulatory route where the blood travels from one organ to another through a vein before reaching the heart (that organ usually does something to the blood  before sending it out).  

  Example: Hepatic portal system - blood from the intestines and stomach goes to the liver for filtering and processing before reaching the heart.
• Major functions of the kidney are filtration and removal of waste, maintenance of electrolytes, acid base balance, and water in the body, and control of BP. 

  How? 

  The kidney filters about 92 L of fluid a day*** (most of it being plasma). It filters it out to produce only 1-2 L of urine. 

  • This means that about 99% of the fluid that enters the nephron must find its way back into the blood. 
• Autoregulation of intrarenal blood flow

  You need adequate blood flow in order to achieve some amount of GFR. 

  We need a good GFR in order for the nephrons to be able to do their function.

  Low mean arterial BP indicates that the kidneys are not necessarily getting enough renal blood flow = not enough blood flow for proper GFR = nephrons cannot do their job effectively.

  
• Processes within the kidney that can affect RBF to increase or decrease GFR: 

  • Salt concentration passing through the distal portion of the nephron 
  • Changes in renin production
• The body does have a certain degree of autoregulatory capacity when it comes to maintaining renal blood flow. 

  We can see if an individual has a mean arterial pressure of somewhere around 80-180 → we are going to see there is a “maintenance”. This says we have a maximum amount of renal GFR with mean arterial BP being 80-100. 

  • Less than that GRF is lower
  • Higher than that it will cause ischemia = reduction in GFR
• Blood flows through glomerulus and ~20% of plasma is filtered through the capillaries of the Bowman’s Capsule. 

  Clinically, we can measure Glomerular Filtration Rate (GFR).

  • GFR should be at least 60 mL/min
  • Values less than 60 usually indicate there is an issue not just with renal blood flow but with GFR in particular → could mean the individual is experiencing some type of renal disease
  • Technically - we like to see GFR around 125, but we have a range 
  • Varies by: 
  • Age → as we get older we tend to have a reduction in GFR 
  • Things like sex, body size, and other factors can also affect it
• GFR takes place in the renal corpuscle (Bowman’s + Glomerulus) which is composed of endothelial cells and other cells that line the bowman’s capsule. 
• Capillary endothelium  

  • The glomerular capillaries are fenestrated → so they have large pores that allow most components of the plasma to filter through the endothelium. However, the pores are small enough to prevent blood cells from leaving the capillary, as well as negatively charged proteins, and especially larger proteins 
• Podocyte

  • In summary → they act like a final filtration barrier with the glomerulus allowing essential fluids to pass through while keeping larger molecules in the blood.
• Capillary endothelium and podocytes work together to control movement of solutes from the plasma into the early portion of the nephron.
• Role in regulation of blood pressure and body fluid. 

  Juxtaglomerular cells (next to the glomeruli)

  • Produce renin 
• Role in regulation of BP and body fluid.

  Maculate densa

  • Line the walls of the DCT
  • They detect changes in Na or NaCl concentrations 
  • In doing so, they affect vascular tone of the efferent arterioles → regulate how much blood flow gets into the capillary and the rate at which it gets released. This helps increase or decrease GFR as needed (by sending a signal that will reduce or increase blood flow to glomeruli itself). 
  • They can also tell the juxtaglomerular cells to make more renin by sending them a signal.
• Juxtaglomerular cells and maculate densa both help regulate BP and fluid volume.

  • b/c the amount of GFR is going to increase or decrease amount of fluid that gets reabsorbed or secreted. 
• Explain RAAS

  A) Renin

  B) juxtaglomerular

  C) ACE

  D) Angiotensin I

  E) liver

  F) Angiotensin II

  G) Aldosterone

  H) Adrenals

  I) decreased

  J) decreased

  
• • In various different segments or geographical locations at the nephron, there are different types of cells
  • Most cells are epithelial cells → polarized cells (meaning they have a top nad a bottom) → participate in transport from one side to the other one (from the apical side to the basal side or vice versa) 
• • The nephron is composed of different types of epithelia which have different function 
  • They may lead to Na reabsorption, Na excretion, and same for Cl, HCO3, and H (all ions will be tightly regulated) 
  • Principal cells → located in the collecting duct
  • Intercalated cells → cells intertwined with other cell types, they help control the amount of water that is in the final urine before making its way out to the renal pelvis (along with the principal cells)
• Realize some processes require passive diffusion → typically they just require some type of gradient. 

  • Ex: water may be passively absorbed as it is in the descending loop of Henle and DCT

  Other things may require active transport → meaning it is working against a concentration gradient. So it needs ATP to facilitate the movement of the ions or water out of the tubular network back into the bloodstream . 

  Also notice, there are many types of ions → Na+, Cl-, H+ (most important), & molecules like NH3, urea, water, HCO3

  • Important: H and HCO3 are important for maintenance of physiologic pH
• In the PCT: most of everything gets reabsorbed.
• • Glomerulus → initial site of filtration 
  • Follows with PCT → reabsorption of ions and water, removing certain types of toxins. 
  • Descending loop of Henle → focuses on water
  • Ascending loop of Henle → Na and Cl reabsorption to maintain adequate water
  • DCT: selectively secretes and absorbs different ions 
  • These ions help maintain pH and electrolyte balance
  • Collecting duct: making final urine and making sure it is concentrated and all the toxins make their way out
• Urine

  It is a filtrate of plasma. Should be sterile (bc we should not be growing bacteria in there). 

  • Normally 1 mL/kg/hr 
  • So someone weighing 70 kgs that has not peed in 3 hours -> you would expect them to usinate 210 mL of urine at minimum 
  • If less than 30 mL/hr, then it is concerning (not an average of 30 mL/hr) 
  • We look at amt of urine to determine how well the kidneys are functioning
• Urine: amber-yellow, clear, pH 4.6-8.0, specific gravity 1.010-1.025 (adults), no blood, no bacteria, no red blood cells, no white blood cells, no crystals, no fat, negative to trace protein.
• Blood urea nitrogen (BUN): 7-18 mg/dL 

  • Less than 20 is okay 
  • It is the amount of nitrogenous waste we have circulating in our bloodstream
• Creatinine: 0.6-1.2 mg/dL

  • Breakdown of muscle metabolism 
  • If lower than 0.6 we don’t worry too much 
  • If above 1.2 then we worry a bit more → because the kidneys are not getting rid of it, it is staying in the blood →: indicating there is an issue with the kidneys  
  • Creatinine is a good indicator of kidney function
• Ureter:

  – From renal pelvis, run about 30 cm in adults and enter posterior bladder wall 

  – Composed of long, intertwined muscle bundles
• Bladder:

  – Smooth muscle fiber

   – Stretch on bladder (250-300 mL) send signal that there is urge to urinate to the internal sphincter which will tell the external sphincter that we need to urinate (external sphincter is a voluntary muscle) → then it will dilate and allow for movement of urine out of the bladder through the urethra 

  • Meaning urination is voluntary bc the external sphincter is a voluntary muscle - we can consciously contract the external sphincter (made of skeletal muscle) to hold urine, even if the bladder is sending signals and the internal sphincter is relaxed (full).
• “over-active bladder” meds > Alzheimer’s 

  • Certain types of medications can lead to overactive bladder bc the medication activates receptors that are located within the muscles that control the movement of urine out of the bladder → leading to people needing to go to the restroom a lot more frequently.
• “Breaking the seal” myth

  • The idea that when an individual is drinking a lot of caffeine or alcohol → once you urinate after consumption of these liquids, you are “breaking the seal” and are destined to urinate more frequently throughout the night. 
  • NOT TRUE. caffeine stimulates sympathetic stimulation → increase GFR → make you want to pee. Alcohol is a diuretic (inhibits ADH) → accumulates water in the collecting duct.
• Urethra

  • Runs from inferior bladder to outside the body 
  • Women 3-4 cm
  • Men 18-20 cm
  • Urethra also passes through the prostate 
  • The prostate is an organ that participates in a variety of things like formation of seminal fluid (fluid that carries sperm cells), etc. D/t geographical location, when it gets enlarged it can impede upon urine flow out the urethra. 
  • Internal sphincter relaxes when bladder is distended 
  • External sphincter is under voluntary control
• Acid/base physio

  Acid-base balance provides a means of assessing homeostasis. 

  Neutral pH is 7

  Predicated on pH: 

  • Acid—H+ ion donor (has a lot of H)
  • pH is less than 7, acidotic or acidic
  • Base—H+ ion acceptor (doesn’t have a lot of H, so it accepts) 
  • pH is greater than 7, alkalotic or alkaline 

  In humans, pH is from 7.35-7.45
• We maintain pH through a lot of different mechanisms. 

  The equation: 

  CO reacts with water to form carbonic acid H2CO3

  Carbonic acid can dissociate (break apart) into a hydrogen ion (H+) and a bicarbonate ion (HCO3-). 

   

  Carbon dioxide → comes from respiration 

  Hydrogen ion concentration → acidic in nature 

  Bicarbonate → produces more alkalosis
• • Chemical buffer systems, prevent large changes in pH 
  • Elimination of CO2 (lungs) 
  • H and HCO3 regulation by kidney

  A lot of our pH is determined based upon factors like the foods we intake bc we produce certain amounts of CO2 and H+ just as a byproduct of metabolizing these foods. 

  Other things that can be produced by food are sulfate, phosphate, chloride, and other types of anions and molecules that will be released or filtered through the kidney → if they are excreted then they are not needed. 
• There are 3 buffering systems

  • Chemical → found primarily in the blood as well as extracellular space. 
  • Example HCO3 buffering some of the activity from H to maintain the pH range 
  • Resp response → conservation or elimination of CO2
  • CO2 is an acid, if we have too much then our pH=low 
  • Manage: increase our RR or depth of respiration
  • Kidney reabsorbs or eliminate ascertain types of ions 
  • Whether or not we excrete a lot of H
  • In the DCT as well as the collecting duct we can eliminate or excrete more H = reduce amount of H in blood
  • Can also increase reabsorption of bicarb (buffer)
• Hydrogen is removed from the blood and put into the urine and excreted, whereas bicarb is reabsorbed from urinary filtrate and placed back into the blood = this helps maintain acid base balance. 
• Physiological pH – 7.35-7.45

  • Alkalotic – >7.45 
  • Acidotic – <7.35

  Physiologic acids and bases

  • PaCO2 – 35 to 45 mmHg

  • HCO3 – 22-26 mEq/L

  Changes in [Acids] or [Bases] will therefore affect pH