BME 2010 Prelim 2 (Musculoskeletal system, Renal system, Endocrine system))

L13: Main components of musculoskeletal system

1. Joints

2. Cartilage

3. Bones

4. Muscle

L13: Components of skeletal system

• Bone (osseous tissue)

  • hard, dense connective tissue that forms most of the adult skeleton

  • support structure of the body

• Cartilage

  • In the areas of the skeleton where bones move (ex: ribcage and joints)

  • Semi-rigid form of connective tissue)

  • Provides flexibility and smooth surfaces for movement

• Joints (a.k.a. articulations)

  • sites where 2 or more bones meet

L13: How bones does the human body have?

206 bones

L13: Bone composition

• Relatively small number of cells entrenched in a matrix of collagen fibers provide a surface for inorganic salt crystals (no carbon) to adhere

• Collagen: highly abundant protein that forms fiber like structure

  • organic, has carbon

• Salt crystals form when calcium phosphate and calcium carbonate combine to create hydroxyapatite, which incorporates other inorganic salts like magnesium hydroxide, fluoride, and sulfate as it crystallizes, or calcifies (becomes hard)

• Hydroxyapatite crystals give bones their hardness and strength, while the collagen fibers given them flexibility so that they are not brittle

  • Calcium I think

  • Probably won’t degrade

L13: Bone types

1. Flat bone

2. Long bone

3. Sesamoid bone

4. Short bones

5. Irregular bone

*Don’t need to remember all of these though

L13: Anatomy of a long bone

Main parts

1. Diaphysis (tubular shaft)

• contains yellow bone marrow filled medullary cavity

2. Epiphysis (wider region at the end)

• contains red bone marrow

3. Metaphysis

• Contains the epiphyseal plate (growth plate)/line

1. Endosteum - lining of the medullary cavity

2. Periosteum - fibrous membrane covering the bone

• Contains blood vessels, nerves, and lymphatic vessels that nourish the bone

L13: Type soft bone tissue: Two types

1. Cortical (compact)

2. Cancellous (trabecular, spongy)

• Compact bone is dense so that it can withstand compressive forces, while spongy bone has open spaces and supports shifts in weight distribution

L14: Bone tissue organization (picture)

L14: Compact bone structure

• Microscopic structural unit of compact bone is called an osteon

• Each osteon is composed of concentric rings of calcified matrix called lamellae

• Running down the center of each osteon is the central canal

  • At the center of the osteons are blood vessels

L14: Spongy bone tissue structure

• Spongy bone tissue contains a network of matrix called trabeculae

• Each trabecula forms along lines of stress to provide strength to the bone

• the spaces of the spongy bone provides balance to the heavy compact bone by making bones lighter so that muscles can move them more easily

• The spaces in some spongy bones contain red marrow

L14: Bone cells

• Bone cells age

• Over time, cells eventually get surrounded by ECM; they get less nutrients and eventually die

Cells with more similar functions

1. Osteogenic cell

   • Stem cell

2. Osteoblast

   • Deposit osteoid (organic matrix)!

     • ECM: includes collagen and minerals

   • regulate mineralization

3. Osteocyte

   • Mature bone cell that maintains the bone matrix

   • Buried, mature osteoblasts

   • Sense and respond to stress

*All derived from osteogenic cells

Cell with different function:

4. Osteoclast

• Bone-resorbing cell

• Fused (multinucleated)

• Secrete acids and proteases to degrade mineralized tissue

*Not derived from osteogenic cells I think

L14: Osteocyte structure

L14: Bone homeostasis and remodeling

• Bone is a dynamic tissue!

• 10% is replaced annually

• Tight controlled process

• Bone resorption (degradation)

• Bone formation (deposition)

• Keeps bone strong

• Osteoblast activity = osteoclast activity

• When osteoclasts resorb damaged, or old bones, calcium is released from the bones into blood circulation; Osteoclast action is regulated by hormones

L14: Osteoporosis

• A disease characterized by a decrease in bone mass that occurs when the rate of bone resorption (degradation) exceeds the rate of bone formation, a common occurrence as the body ages

• Histologically, osteoporosis is characterized by a reduction in the thickness of compact bone and the number and size trabeculae in the cancellous bone

• A bit of osteoporosis might happen with age

L14: Bone and gender and ageing

• Women lose bone mass more quickly than men starting at about 50 years of age (around menopause)

• Ovaries reduce in size and cease the production of estrogen, a hormone that promotes osteoblastic activity and production of bone matrix; Thus, osteoporosis is more common in women than in men

L14: Physical factors

• Bone remodeling is affected by mechanical stress (muscle pull, gravity)

• Wolff’s law: Bones will adapt based on the stress or demands placed on them

• When you work your muscles, they put stress on your bones; In response, your bone tissue remodels and becomes stronger

• If you don’t use the muscles surrounding a bone much, the bone tissue can weaken

L14: Joints (articulations)

• The human body has 206 bones, and with the exception of one, each bone is connected to at least one other bone; Sites sites where 2 or more bones meets are the joints

• Bones articulate with each other (join together)

• Many joints allow for movement between between the bones, at these joints bones can move smoothly over another

• Conversely some joints, have little or no mobility, are strongly united to each other; example? (see next card)

  • probably fibrous

• At other joints, the bones are held together by cartilage, which permits limited movements between the bones

*One bone is a floating bone (only stuck to cartilage - hyoid bone)

L14: Classes of joints

• Synovial (freely mobile)

• Fibrous (mostly immobile)

• Cartilaginous (limited mobility)

• Greater mobility → lower stability

L14: Synovial joints

• Most common type of joint in the body

• A key structural characteristic for a synovial joint is the presence of a joint cavity

• This fluid-filled space is the site at which the articulating surfaces of the bones contact each other

• The articulating bone surfaces at this joint are not directly connected to each other; Allowing bones to move smoothly against each other, resulting in increased joint mobility

*Can be uniaxial, biaxial, multiaxial

L14: Components of Synovial Joints

• Articular capsule: The articular capsule surrounds the joint and is continuous with the periosteum of articulating bones; it consists of two layers

  • Fibrous layer (outer) consists of white fibrous tissue, known as the capsular ligament. It hold together the articulating bones

  • Synovial membrane (innter): Thin lining of the inner surface of the articular capsule; secrete synovial fluid; thick slimy fluid that lubricates the joint

• Articular cartilage: a thin layer of hyaline cartilage that covers the entire articulating surface of each bone; prevents friction (like a cushion)

  • Note: most of the problems occur in the articular cartilage (wear and tear - osteoarthiritis)

L14: Types of Synovial Joints

• Six types in total

• The synovial joint with the greatest range of motion is the ball-and-socket joint

• At these joints, the rounded head of one bone (the ball) fits into the concave articulation (the socket) of the adjacent bone

• The hip joint and the shoulder joint are the only ball-and-socket joints of the body

L15: Disease focus: Osteoartiritis

• degenerative joint disease

• particularly affects weight-bearing joints

• leading cause of disability in the elderly

L15: Disease focus: Osteoarthritis (continued)

• Common disorder of synovial joints: involves inflammation of the joint; Often results in significant joint pain, along with swelling, stiffness, and reduced joint mobility

• Stress on the articular cartilage that covers the surfaces of bones at synovial joints, causes the cartilage to gradually become thinner; as the articular cartilage layer wears down, more pressure is placed on the bones

• the joint responds by increasing production of lubricating synovial fluid, but this can lead to swelling of the joint cavity, causing pain and joint stiffness as the articular capsule is stretched

• No cure for osteoarthritis (can’t reverse it): treatments may include lifestyle change, such as weight loss and low-impact exercise, and over-the-counter or prescription medications that help to alleviate the pain and inflammation; For severe cases, joint replacement surgery (arthroplasty) may be required

L15: Cartilage functions

• Structural support: structure in the external ear, and the tip and septum of the nose

• Protection: Acts as a shock absorber, cushioning areas where bone meets bone and preventing abrasion and damage

• Movement: a joint would not be able to bend without the flexibility of cartilage

• Bone growth and regeneration: Cartilage also plays a role in bone growth and repair, as in the embryo, it provides a template for ossification (process of bone formation)

  • Cartilage is mineralized → bone (primer for bone tissue)

*Cartilage is a tissue: cells + ECM

L15: Composition of cartilage

Specialized cells:

1. Chondroblasts: Produce matrix components; Eventually become chondrocytes

2. Chondrocytes: Immobile form of chondroblasts; Surrounded by the matrix and contained within lacunae

Structural extracellular matrix that contains:

1. Collagen (protein, can be of different types)

• provides form

• resists tension

• (not able ot retain water)

2. Hyaluronan (Glycosaminoglycan, polysaccharide compound)

• Retains water (80%)

• Resists compression

• (provides flexibility)

*Can change amounts of collagen and hyaluronan in cartilage

L15: Types of cartilage found in human body

• Hyaline cartilage

  • Most common type of cartilage in your body

  • Translucent, slippery and smooth

  • Hyaline cartilage locations in your body include:

    • 1. Synovial joints

    • 2. Trachea

  • Part covering bone

• Fibrocartilage:

  • Tough cartilage made of thick fibers; the strongest and least flexible (toughest)

  • Fibrocartilage locations in your body include

    • Tendons and ligaments

• Elastic cartilage:

  • Most flexible cartilage; supports parts of the body that needs to bend aand move to function; Elastic cartilage can bounce back to its original shape

  • Elastic cartilage locations in your body include:

    • External ears (the parts of the ear that are outside your body)

    • Larynx (voice box)

L15: Muscle

Functions:

• Movement

• Effector organs of the nervous system

Key characteristics:

• High energy demanding tissue: cell metabolism is critical

• Consist of excitable cells (sense electricity)

• Under the control of nervous system

Types:

1. Skeletal

2. Smooth

3. Cardiac

Muscles store energy in the form of glycogen!!

L15: Structure of skeletal muscle

• Generally connected to 2 or more bones

• Connected to bones via tendons (cords of connective tissue that transmit force from muscle to bone)

*Type of cartilage!

L15: Structure of skeletal muscle from macro to micro level

Muscle → fascicle → muscle fiber → myofibril → filaments (very organized)

• muscle fiber is the cell, made up of myofibrils

L15: Muscle fiber structure

L15: Muscle fibers

• Muscle Fibers = each is an individual cell

• Very large cells (10-100um diamater)

• Multinucleated

• Innervated (one motor neuron)

• Sarcolemma = Plasma membrane

1. Sarcolemma: Plasma membrane (it’s the cell membrane)

2. Sarcoplasm: semi-fluid cytoplasm

3. Sarcoplasmic reticulum (SR)

   • Specialized smooth ER

   • Network surrounding myofibrils

   • Associated with Transverse (T) tubules - like ER but also has (T) tubules

   • Lateral sacs are parts of the SR that store calcium ions

   • Triad: each tubule associated with two lateral sacs

• Contain bundles of protein filaments called myofibrils

L15: Myofibrils

• Makes up muscle fiber

• Contractile bundles of myofilaments

• Thin filament: actin

• Thick filament: myosin

• Thick and thin filaments together form sarcomeres (fundamental unit of myofibrils)

L15: Thin Filaments - Components

1. Actin

   • Contractile protein

   • Smallest funcitonal unit - G-Action (“bead”)

   • G-Actin has a myosin binding site (black dot)

2. Tropomyosin

   1. Regulatory protein

   2. Surrounds F-actin (“string of beads”) and covers up the myosin binding site

   3. Different from myosin!

3. Troponin complex

   1. Regulatory protein

   2. Complex made of 3 proteins that binds to actin strang, tropomyosin, and calcium, respectively

L15: Thick Filaments Components

Myosin

• Myosin Dimer consisting of a head and tail

• Two myosin molecules are bound at the tail ends

• Myosin head has an Actin binding site and an ATPase site; Myosin heads are called crossbridges

  • head must stick out: bind to actin and also has ATPase

  • ATP is hydrolized by ATPase I think → energy is released

Titin protein:

• highly elastic protein

• each of the “beads” = G-actin binds to myosin

• Thick and thin filaments bind to each other

L15: Sarcomere

Sarcomere: Fundamental contractile unit of muscle fibers

A band:

• Dark band

• Thick filaments

• Overlap with thin

H zone:

• Thick filaments

• No overlapping

M line:

• Links thick filaments

I band:

• Light band

• Thin filament

• No overlapping

Z line:

• Links thin filaments

L16: The mechanism of muscle contraction

Upon contraction (passing electricity through):

• H zone shortens

• A band remains the same (as the relaxed muscle)

• Z line came closer

L16: Sliding filament model

• During contraction, thin filaments (actin filaments) slide closer inwards)

• Sliding is due to cyclical formation and breaking of crossbridges = crossbridge cycle

L16: Crossbridge cycle

• Mechanism that drives sliding of thick and thin filaments past each other is back and forth motion of myosin crossbridges powered by ATP hydrolysis

• Back and forth motion of crossbridges is due to chang ein the conformation of myosin molecules

  • myosin goes from high-energy form (has stored energy) to low-energy form (released energy)

L16: The crossbridge cycle (image)

*Need Ca2+ for step 1

L16: The cross-bridge cycle (continued)

• Crossbridges at the opposite ends of thick filaments are oriented in opposite directions from each other

  • power strokes of the crossbridges at the opposite ends move in opposing direction pulling the thin filaments towards the center

• At the end of the crossbridge cycle, the thin filaments passively slide back to their original position

L16: Muscle fiber contraction - very fast!

• Thousand sof power strokes can happen per second —> muscle fiber can contract fully in less than a tenth of a second

L16: Excitation-contraction coupling

How muscle contractions are turned on and off by the CNS via motor neurons

• Want to contract only when it gets signal by nervous system; not when it has ATP

L16: CNS-mediated regulation of muscle fiber contraction

• Motor neurons deliver the commands to skeletal muscles telling them when to and when not to contract

• Muscle cels are excitable → capable of generating action potential (AP)

• After receiving input from motor neuron → muscle cell depolarizes → fires an AP

• Sequence of AP to the contraction is referred to as excitation-contraction coupling

L16: Muscle fiber stucture w/ neuromuscular junction (image)

Nerve ending binding to muscle fiber

L16: Neuromuscular junction in more detail (image)

L16: Neuromuscular junction in more detail explanation; excitation-contraction coupling

Excitation-contraction coupling

• Neuromuscular junction is similar to a synapse

• AP travels through motor neuron (presynaptic cell) into neuromuscular junction → releases acetylcholine (ACh) → diffuses to the muscle cell (postsynaptic cell)

• Specialized region of sarcolemma → motor end plates contain many ACh receptors → resulting depolarization (end plate potential) is amplified causing an AP in the muscle cell

• AP propagates through the sarcolemma down the T tubules releasing calcium from sarcoplasmic reticulum (SR) that initiates the crossbridge cycle

L16: Relaxed Muscle vs. Contracting muscle

Relaxed muscle:

• Concentration of calcium is low in cytosol there is no binding of calcium to troponin

• Tropomyosin positioned on actin filaments blocking myosin binding sites

  • Note: actin filaments is like a helix, like two intertwined pearl strings

Contracting muscle

• AP travels to T tubules → Calcium channels in SR open and release calcium

• Calcium binds to the protein troponin complex → change in conformation of troponin complex → tropomyosin moves from resting position → Myosin binding sites exposed

• Myosin heads can now bind actin and crossbridge cycle can begin

L16: Binding of Troponin to calcium

• Binding of Troponin to calcium is a reversible reaction

• Calcium voltage channels close when membrane potential in the SR is back to normal

• Closure of calcium channels turns off release of calcium and enhances active transport back into SR → Calcium is cleared from the cytosol

  • teh active transporters are present in the SR

• Calcium dissociates from troponin → both troponin and tropomyosin revert to resting positions → Myosin binding site not exposed → decline in number of active crossbridges → eventually muscle contraction ends

L17: Purpose of Urinary (Renal) system

• Waste management

• Maintain blood composition

• Maintain osmolarity of blood

L17: Structure of the Urinary system (image)

L17: Macroscopic anatomy of the kidney (image)

L17: Microscopic anatomy of the kidney

Capillaries interact with the nephrons

L17: Microscopic anatomy of the kidney: Nephron

the blood is processed through the nephrons

L17: Blood supply to the kidney

• Renal arteries supply blood to kidneys

• Within the kidney the renal artery branches into smaller arteries

  *The renal arteries supply oxygenated blood

L17: Blood supply to kidney (memorize this pathway!)

Afferent arteriole → Glomerular Capillary bed → Efferent arteriole → Peritubular capillaries → Vasa Recta

L17: Blood supply to kidney (more in-depth)

• Interlobular arteries divide further into afferent arterioles that form the glomerular capillary bed, which interact with the nephron

• Coming out of the glomerular capillary bed in the efferent arteriole

• Efferent arteriole: gives rise to second capillary bed Peritubular capillaries and Vasa recta; these capillaries drain into veins

*Use acronym AGE:

A = Afferent

G = Glomerulus

E = Efferent

L17: Portal system

Portal system: two capillary beds joined in series

L17: Juxtaglomerular apparatus

• Plays an important role in maintaining blood pressure and blood volume

• Granular cells on the wall of the arteriole contain renin (an enzyme)

*The afferent arteriole looks bigger than the efferent arteriole

*In this case: in the nephron, most of interaction w/ blood happens in the bowman’s capsule

L17: Composition of blood

Plasma:

• 90% water

• 10% made up of ions, proteins (~7%), dissolved gases, nutrient molecules, and wastes

• In the kidneys, water and solutes are exchanged between blood plasma and fluid in the renal tubules to regulate the composition of plasma

L17: Basic renal exchange process

3 exchange processes occur in the nephron:

1. Glomerular filtration: Flow of protein free plasma from glomerular capillaries into Bowman’s capsule

2. Reabsorption: selective transport of molecules from renal tubules to peritubular capillaries, then returned to general circulation

3. Secretion: Selective transport of molecules from peritubular capillaries into renal tube

*Excretion: elimination of materials from tubules out of body

L17: Glomerular filtration

Glomerular Filtration is driven by Starling forces

• Starling forces: forces that drive the movement of fluid in and out of capillaries

• Determined by:

  • 1. Hydrostatic forces (force blood exerts on its vessel wall)

  • 2. Osmotic pressure gradients

• Filtrate resembles plasma in composition except it lacks the cells and proteins found in plasma

L17: Glomerular filtration (continued)**

The sum of Starling forces in the renal corpuscle is called glomerular filtration pressure

4 forces play key role in glomerular filtration:

1. Glomerular capillary hydrostatic pressure (P_GC): favors filtration and is equal to blood pressure of glomerular capillaries = 60 mm Hg

   • Hydrostatic pressure increases because efferent radius is smaller than afferent radius

2. Bowman’s capsule osmotic pressure (π_BC): favors filtration; very little protein in the filtrate hence osmotic pressure is negligible under normal conditions (π_BC) = 0 mm Hg

   • high protein concentration pulls plasma towards it, but there’s no protein → would have favored, but doesn’t exist

3. Bowman’s capsule hydrostatic pressure (P_BC): Opposes filtration = 15 mm Hg

4. Glomerular osmotic pressure (π_BC): Opposes filtration; presence of proteins in the plasma tends to draw filtrate back; Approximately 29 mm Hg

L17: Recap of Glomerular filtration pressures

1. Glomerular capillary hydrostatic pressure (P_GC) = favors filtration, 60 mm Hg

2. Bowman’s capsule osmotic pressure (π_BC): favors filtration = 0 mm Hg

3. Bowman’s capsule hydrostatic pressure (P_BC): Opposes filtration = 15 mm Hg

4. Glomerular osmotic pressure (π_BC): Opposes filtration = 29 mm Hg

Net number = 60 - (15 + 29) = 16 mm Hg

L17: Glomerular filtration (wall of bowman capsule and renal tubule)

• wall of bowman capsule and renal tubule are made up of epithelial cells

• In the Bowman’s capsule this epithelium folds on itself to envelope the glomerular capillaries

• Glomerular filtrate must cross 3 barriers:

  • 1. Capillary endothelial cell

  • 2. Basement membrane

  • 3. Bowman epithelial cell

• Together this is the glomerular membrane or filtration barrier

• Structure favorable for bulk flow due to presence of slit pore and fenestration

L18: Recap of anatomy of the kidney

L18: Glomerular filtration rate, filtration fraction, filtered load of a solute

Glomerular filtration rate:

Under normal conditions,

• Renal plasma flow = 625 mL/min (plasma flowing through kidney/min)

• Volume of plasma filtered per unit time, glomerular filtration rate (GFR) = 125 mL/min = 180 L/day!

Filtration fraction

• Fraction of renal plasma volume that is filtered is the filtration fraction

• Filtration fraction = GFR/renal plasma flow = 125mLmin^-1/625 mLmin^-1 = 0.2 = 20%

• 20% of the plasma that flows into the kidney is filitered into the Bowman’s capsule

Filtered load of a solute

• quantity of a particular solute filtered per unit time

  • Filtered load = GFR x P_x

  • Where P_X is the plasma concentration of X

L18: Regulation of GFR and mechanism

Regulation of GFR

• Changes in GFR are undersirable = change urine flow = interferes with kidneys’ ability to regulate plasm avolume and composition

Mechanisms of GFR regulation:

1. Myogenic regulation of GFR

2. Tubuloglomerular feedback

L18: Myogenic regulation of GFR

• When Mean arterial pressure (MAP) increases pressure in afferent arteriole increases causing its walls to stretch

• Smooth muscle in wall of afferent arteriole contracts in response to stretch

• When these walls contraction, they is increase in resistance reducing blood flow

• Reduced blood flow in afferent arteriole reduces the glomerular capillary pressure

L18: Tubuloglomerular feedback

L18: Reabsorption

(refer to previous diagrams too)

• Movement of solutes and water from renal tubule into blood plasma

• Some solutes are reabsorbed conpletely

• Others are regulated to vary their excretion rate

• Many solutes are reabsorbed actively

L18: Reabsorpotion (continued)

• Sending things back into circulation

• Solute reabsorption mostly occurs in proximal and distal convoluted tubules

• Peritubular space: space between peritubular capillary and renal tubule - filled with interstitial fluid

• Barrier for reabsorption

  • 1. Tubule epithelial (primary barrier)

  • 2. Capillary endothelial cell (barrier only to proteins, cells)

L18: Mechanism of solute reabsorption

Active reabsorption of solute

• Both X and Y are actively transported. But different mechanisms

  • 1. Active transporter for X located on apical membrane → X gets actively transported into the cell → high intracellular concentration of X → moves into peritubular space by facilitated diffusion & then diffuses into plasma

  • 2. Active transporter for Y located on basolateral membrane → Y gets actively transported into peritubular space → diffuses into plasma; lower intracellular concentration of Y → facilitated diffusion of Y into cell

L18: Mechanism of water reabsorption

• Based on osmolarity

• As X and Y get reabsorbed into plasma → increase in osmolarity of plasma → water diffuses down its concentration gradient into region of high osmolarity

• Passive

L18: Mechanism of solute and water reabsorption: Passive reabsorption

• Z is passive reabsorbed

• Two conditions must be met

1. [Z] must be greater in tubular fluid

2. Z must be able to permeate tubular and capillary membrane

• When most of H₂O is reabsorbed, [Z] ↑ in tubular fluid whereas [Z] ↓ in plasma (Remember tubular fluid came from plasma)

L18: Recap: Active solute reabsorption, water reabsorption (passive), and Passive solute reabsorption via diffusion comparison

L18: Transport maximum

• When solutes rae transported from filtrate to plasma, the carrier proteins and pumps can get saturated

• When solute concentration is high enough, all carrier porteins and pumps are occupied, and the system is operating at transport maximum

  • Probably not the same as renal threshold which is the specific blood concentration of a substance (like glucose) above which the kidneys start excreting it into the urine?

L18: Transport maximum: Relevance in Glucose reabsorption

• Glucose if freely filtered at glomerulus

• 100% actively reabsorbed in proximal tubules

• Normally no glucose appears in urine

• If plasma concentration of glucose increases → filtrate concentration high→ pumps and carriers get saturated → glucose spillover into urine

• 1

• 100 mg/dL = normal value of concentration of glucose in plasma

L18: Diabetes Mellitus and Nephropathy

• In Diabetes Mellitus [Glucose] in plasma is elevated (hyperglycemia) → glucose appears in the urine

• Affects water reabsorption into plasma

  • Causes thirst and excessive urination in patients

• 20-30% patients of D< also develop Diabetic nephropathy

  • High [Glucose] damage the nephrons

L19: Secretion

• Solute moves from peritubular capillaries into renal tubule

• Barriers are same as reabsorption

• Transport mechanisms are the same, but in the opposite direction

• Secreted substances (examples)

  • Potassium

  • Hydrogen ions

  • Choline

  • Creatinine

  • Penicillin

• Secretion increases [solute] in urine and decreases [solute] in plasma

L19: Regional specialization of the renal tubules

• tubule epithelium varies from region to region → substance transported, and mechanism of transport differ

Proximal tubule

• Non-regulated reabsorption in the proximal tubules

  • Highly folded apical membrane = large surface

  • Cells possess large no. of mitochondria = large ATP supply

  • Tight junctions in the epithelia are leaky

Distal tubules and collecting ducts

• Regulated reabsorption and secretion in the distal tubules and collecting ducts

  • tight epithelium

  • Cells have receptors for hormones that regulate absorption

    • reabsorption/secretion only happen when needed

L19: Excretion rate of a solute

When filtrate is excreted = urine

• Materials that enter the lumen of the renal tubules is excreted unless it is reabsorbed

**Amount excreted = Amount filtered + amount secreted - amount reabsorbed

• E = F + S - R

Excretion depends on 3 factors:

1. Filtered load (F)

2. Rate of solute secretion (S)

3. Rate of reabsorption (R)

L19: Renal processing of a hypothetical solute and water (image)** pay extra attention

L19: Renal processing of solute

Comparing filtered load with amount of solute excreted/min → net effect of renal processing of that solute

1. If amount of solute excreted per minute is less than filtered load = net reabsorption of the solute occurred

2. If amount of solute excreted per minute is greater than filtered load = net secretion of the solute occurred

• Only net effect can be determined. Cannot decouple reabsorption and secretion

• Can only tell which is greater - secretion or reabsorption

L19: Clearance (of a solute)

• The volume of plasma from which a substance is completely removed (cleared) by kidneys per unit tiem

• Clearance depends rate of excretion of the solute and the concentration of solute in plasma

Clearance = Excretion rate/Plasma concentration

*Plasma concentration is concentration of X

L19: Clearance (calculations)

• Excretion rate = 9 mmol/min = 540 mmol/hr

• Px = 0.08 mmol/mL = 80 mmol/L

• Clearance = 540 mmolhr^-1 /80 mmolL^-1= 6.75 Lhr^-1

• 6.75 L is the hypothetical volume of plasma that is cleared of the solute in an hour

L19: Clinical use of clearance

• Clearance = Excretion rate / Plasma concentration

• Product of urinary concentration of a solute x, (U_x) and urine flow rate (V) gives the Excretion rate = U_x x V

• P_x is plasma concentration

Clearance = (U_x x V)/P_x

L19: In certain cases clearance provides an estimate of GFR

• Clearance can be used to determien GFR if a substance is freely filtered and is neither reabsorbed nor secreted, then amount in urine is equal to amount filtered = filtered load

• Under these conditions the substance is cleared from the volume that was filtered, thus we can say clearance = GFR

• Inulin, a polysaccharide meets these requirements

  • Inulin is neither secreted nor reabsorbed

  • Amount of inulin excreted in urine = amount that was filtered = filtered load

  • So clearance of inulin = GFR

L19: Clearance estimation using Creatinine

Creatinine: product of muscle metabolism (gets secreted a little bit)

• Use of creatinine to estimate GFR is non-invasive

• Creatinine: by-product of muscle metabolism

• Produced in body

• Freely filtered

• Not reabsorbed

• Clearance: suitable clinical “estimate” of GFR

• Because a small amount of Creatinine is secreted clearance of Creatinine is a little greater than GFR

L19: Clearance can also determine fate of solutes

• If C_x > GFR, then net secretion of the solute occured

• If C_x < GFR, then net reabsorprtion of the solute occurred

L19: Renal Endocrine system crosstalk

• When blood pressure falls, juxtaglomerular cells release the enzyme Renin into your bloodstream

• Renin cleaves angiotensinogen, a protein your liver makes, making angiotensin I

• Angiotensin I, which is inactive, is cleaved by angiotensin-converting enzyme (ACE), into angiotensin II, an active hormone

• Angiotensin II triggers Adrenal glands to release hormone Aldosterone

• Aldosterone cause your kidneys to reabsorb sodium and secrete potassium. The increase in sodium in your bloodstream causes water retention. This increases blood volume and blood pressure, thus completing the renin-antiotensin-aldosterone system

L20: Recap: estimating GFR using clearance

L20: Adrenal glands

• Also called Suprarenal glands

• Comprises of 2 layers

  • 1. Outer layer - Cortex

  • 2. Inner core - Medulla

• Adrenal cortex secretes adrenocorticoids. example: aldosterone and cortisol

• Cortisol regulates the body’s response to stress; stimulates gluconeogenesis

L20: Endocrine system (image)

L20: Endocrine system overview

• Organs of endocrine system are the endocrine glands

• Endocrine glands are a group of cells that secrete hormones

• Hormones allow cell to cell communication (like neurotransmitters but the signaling is slower)

Two types of endocrine glands:

1. Primary endocrine gland: primary function is hormone secretion

• ex: Hypothalamus, thymus, pancreas, etc.

2. Secondary endocrine gland: hormone secretion is a secondary function

• ex: stomach, kidney, skin, etc.

L20: Autocrine, Paracrine, Endocrine signaling

• Autocrine: signal the same cell

• Paracrine: signal nearby cells

• Endocrine: signal cells far away

L20: Hypersecretion vs. Hyposecretion

• Hyposecretion: Too little

  • ex: Diabetes mellitus type 1

  • Caused due to insufficient insulin

• Hypersecretion: Too much

  • ex: Acromegaly

  • Caused due to too much growth hormone in adults

L20: List of Primary Endocrine Glands

• Hypothalamus and pituitary gland

• Pineal gland

• Thyroid gland

• Parathyroid gland

• Adrenal glands

• Pancreas

• Gonads

L20: Hypothalamus and Pituitary gland

• Together they regulate almost every body system

• Hypothalamus secretes several hormones, most of which affect the pituitary gland

• Pituitary gland (aka hypophysis) consists of two parts:

  • 1. Anterior lobe (adenohypophysis): derived of epithelial tissue

  • 2. Posterior lobe (neurohypophysis): derived of neural tissue

L20: Hypothalamus and the posterier pituitary gland

• Two types of neurohormones secreted by hypothalamus into posterior pituitary:

  • 1. Antidiuretic hormone (ADH): aka vasopressin

    • decreases urine output

    • ADH release stimulated by solute concentration in blood → regulates water reabsorption → targets cell in the nephron, maybe more specific parts?

  • 2. Oxytocin

    • stimulated by pressure in the uterus or baby sucking → targets cells in the breast and uterus

    • Stimulates pressure in uterus to help birthing, also lactation

L20: Hypothalamus and anterior pituitary

• Cells in the hypothalamus that control the anterior lobe secrete tropic (or trophic) hormones

• Trophic hormones: hormones that regulate the control of other hormones

  • can be stimulatory

  • can be inhibitory