BME2010 Prelim #2

The sheer amount of memorization here is gonna kill me bro

Musculoskeletal System Main Components

Joints, cartilage, bones, muscle

Skeletal System

Made of bones and joints

Osseous Tissue

Bone. Hard, dense, connective tissue that forms majority of skeleton

Joints

Articulation sites where 2 or more bones meet. Have cartilage for connective tissue and lubrication

Bone Composition

Relatively few cells with inorganic salt crystals latching to dense matrix of collagen fibers

Collagen

Highly abundant fiber-like protein

Hydroxyapatite Crystals

Hard inorganic salt crystals that give bones their hardness, includes calcium phosphate, calcium carbonate, + other salts like magnesium hydroxide, fluoride, etc.

Calcification

The crystallization process that turns inorganic salts into the bone crysals

Types of Bone Tissue

Cortical (compact), cancellous (trabecular, spongy)

Compact Bone

Dense, can withstand compressive forces. Made up of many osteons

Osteon

Composed of concentric rings of calcified matrix called lamellae, has a central canal running down center which provides nutrients + flow

Cancellous (spongy, trabecular) Bone

Made of lattice-like network of matrix called trabeculae, which form along lines of stress to provide strength. Contain red marrow

Bone Type Purpose

Spongy bone balances heavy compact bone, maintaining strength while making bones lighter so muscles can move them easier

Types of Bone Cells

Same family: osteogenic, osteoblast, osteocyte

Other: osteoclast

Osteogenic Cells

Stem cells for bones

Osteoblast

Matrix synthesizing cell, responsible for bone growth and regulating mineralization

Osteocyte

Mature bone cell that maintains the matrix, buried, sense + respond to stress

Osteoclast

Fused, multinucleated cell that secretes acids + proteases to degrade mineralized tissue

Bone Homeostasis

Bone is dynamic tissue, ~10% replaced annually. Osteoclasts resorb, osteoblasts deposit, keeps bone strong. Regulated by hormones since calcium levels affected by osteoclasts

Osteoporosis

Disease characterized by decrease in bone mass, happens when resorption rate exceeds formation rate. Compact bone thinner, trabeculae more porous. Common as body ages.

Osteoporosis by Gender

Osteoporosis is more common in women than men, especially starting at ~50 years after menopause

Trabeculae Formation

Form along lines of stress to strengthen bone

Wolff’s Law

Bones adapt based on stress/demands placed on them

Joints

Connections between bones, many provide movement, some have little/no mobility. All but 1 bone connected to joint

Joint Classes

Synovial, fibrous, and cartilaginous

Synovial Joints

Most common type, bones not directly connected, allows articulation via joint cavity

Joint Cavity

Fluid filled space where articulating surfaces contact.

Synovial Joint Components

Articular capsule (fibrous outer layer, synovial membrane inner layer) and articular cartilage

Articular Cpasule

Surrounds the joint, continuous with outside of articulating bones, made of fibrous outer layer and synovial membrane inner layer

Fibrous Outer Layer

Made of capsular ligament, white fibrous tissue that holds together articulating bones

Synovial Membrane

Thin lining of the inner surface of articular capsule, secretes synovial fluid which lubricates joint

Articular Cartilage

Thin layer of hyaline cartilage that covers articulating surface of bones, preventing friction.

Types of Synovial Joints

Pivot, hinge, saddle, plane, condyloid, and ball-and-socket

Osteoarthritis

Degenerative joint disease on weight-bearing joints, leading cause of disability in elderly. Happens when articular cartilage wears down → more pressure on bones → more synovial fluid → swelling. No cure

Cartilage Functions

Structural: Structure in external ear, septum, and nose

Protective: Shock absorber, cushion bone + prevent abrasion

Movement: Allows joints to bend

Growth + Regeneration: Provides template for bone growth

Cartilage Cells

Chondroblasts: produce matrix components, become chondrocytes

Chondrocytes: Immobile form of chondroblasts, surrounded by matrix and lacunae

Cartilage Structural ECM

Collagen protein, Hyaluronan polysaccharide compound

Hyaline Cartilage

Most common type in body. Translucent, slippery, smooth. found in synovial joints and trachea

Fibrocartilage

Tough, made of thick fibers. Strongest, least flexible, found in tendons + ligaments. Type I collagen

Elastic Cartilage

Most flexible, found in external ears and larynx (voice box). Mainly type II collagen.

Muscle

Movement + effector organs of nervous system, high energy demand, excitable cells controlled by nervous system

Types of Muscle

Skeletal, smooth, cardiac

Skeletal Muscle Structure

Connected to 2 or more bones via tendon

Skeletal Muscle Structure Cascade

Muscle → fascicle → muscle fiber → myofibril → filaments

Muscle Fibers

Large (10-100μm) multinucleated cells, innervated (one motor neuron), contain bundles of protein filaments called myofibrils

Muscle Fiber Components

Sarcolemma: plasma membrane

Sarcoplasm: semi-fluid cytoplasm

Sarcoplasmic Reticulum (SR): specialized smooth ER network surrounding myofibrils, store calcium ions in lateral sacs, align in triad with transverse tubules

Myofibrils

Contractile bundles of myofilaments made of thin actin filament and thick myosin filament, come together to make sarcomeres

Sarcomeres

Fundamental unit of myofibrils, made of thin and thick filaments coming together

Thin Filament Components

Actin, tropomyosin, troponin complex

Actin

Contractile protein, smallest functional unit is G-Actin which has a myosin binding site

Tropomyosin

Regulatory protein surrounding F-actin to cover myosin binding site

Troponin Complex

Regulatory protein made of 3 proteins that bind to actin strand, tropomyosin, and calcium

Thick Filament Components

Myosin and titin protein

Myosin

dimer made of head and tail, two myosin dimers bind with tail at both ends, those bundle for thick filament. Myosin head (crossbridge) has actin binding site and ATPase

Sarcomere Bands

A band: dark, thick + thin filament overlap

H zone: thick filaments

M line: links thick filaments

I band: light band, only thin filament

Z line: links thin filaments

Mechanism for Muscle Contraction

Sliding filament model, muscles contract because thick and thin filaments slide into each other

The Crossbridge Cyccle

Mechanism that drives thick and thin filaments to slide back and forth, via ATP-powered crossbridges

The Cross Bridge Cycle

1. Myosin binds to actin

2. Power stroke, actin pulled to middle

3. ADP released, myosin enters rigor low energy form

4. Unbinding of myosin and actin via ATP binding

5. Myosin head is cocked into high-energy form via ATP hydrolysis

Power Stroke Frequency

Thousands of times per second

CNS-Mediated Muscle Fiber Contraction

Motor neurons send to skeletal muscle → generate AP after receiving input and depolarizing → excitation-contraction coupling

Excitation-Contraction Coupling

AP in neuron reaches neuromuscular junction (synapse) → release and diffuse acetylcholine (ACh) → AP fired along sarcolemma & down T tubule → Ca2+ released from sarcoplasmic reticulum → Ca2+ allows crossbridge cycle → Ca2+ actively transported back to SR

Ca2+ for Muscle Contraction

Ca2+ binds to troponin complex → shifts tropomyosin which is blocking myosin binding sites, now exposed → crossbridges can now bind to myosin binding sites

Calcium Removal from Muscle

Calcium release is voltage gated, but when repolarizing active transport moves calcium back into SR, clearing it from cytosol. This resets troponin and tropomyosin.

Renal System Components

Kidney, renal vein, renal artery, ureter, bladder, urethra

Macroscopic Kidney Anatomy

Renal cortex → renal medulla → renal papilla → major calyx → minor calyx → renal pelvis

Microscopic Anatomy of the Kidney

Renal pyramids stretch cortex, medulla, and calyx, contain nephron

Nephron

Main filtering mechanism in the kidneys

Renal corpuscle → proximal convoluted tubule → proximal straight → loop of Henle → distal convoluted tubule → collecting duct

Renal Corpuscle

Contains glomerulus, fed through afferent → efferent arteriole, which is surrounded by Bowman’s capsule

Blood Supply to Kidney

Renal arteries supply blood, within kidney artery branches into smaller arteries. Branches down from renal artery to arterioles, then collects back to renal vein

Glomerular Capillary Bed

Surrounds nephron, efferent arteriole exits from it and feeds peritubular capillaries and vasa recta. Creates portal system.

Juxtaglomerular Apparatus

Site of exchange between glomerulus and Bowman’s capsule, feeds into branching glomerular capillaries and made of granular (juxtaglomerular) cells

Renal Exchange Process

Glomerular filtration → reabsorption → secretion

Glomerular Filtration

Flow of protein-free plasma from glomerular capillaries into Bowman’s capsule. Driven by Starling forces determined by hydrostatic and osmotic pressure gradients

Glomerular Filtrate

Resembles plasma in composition, however no cells/proteins like are found in plasma

Glomerular Filtration Pressure

Sum of Starling forces, playing a major role in speed of filtration

Starling Forces

Glomerular capillary hydrostatic pressure (P_GC): blood pressure of capillaries, favors filtration (=60 mmHg)

Bowman's capsule osmotic pressure (π_BC): favors filtration but little protein in filtrate so negligible (=0 mmHg)

Bowman's capsule hydrostatic pressure (P_BC): pressure of bowman capsule, opposes filtration (=15 mmHg)

Glomerular osmotic pressure (π_GC): proteins in plasma draw filtrate back, opposes filtration (= 29 mmHg)

Net: 16 mmHg favoring filtration

Glomerular Filtration Barrier

Glomerular filtrate must cross

1. capillary endothelial cell

2. basement membrane

3. Bowman epithelial cell

Glomerular Filtration Barrier Structure

Favorable to bulk flow due to slit pore and fenestration, due to podocyte banded structure

Normal Condition GFR

125 mL/min, 180 L/day

Filtration Fraction

Fraction of renal plasma volume filtered

(GFR) / (Renal Plasma Flow) = ~20%

Filtered Load of Solute

Quantity of a solute filtered per unit time

Filtered load = GFR * P_x

Regulation of GFR

GFR changes are undesirable because they interfere with kidney’s ability to regulate plasma volume + composition

Mechanisms of GFR Regulation

1. Myogenic regulation of GFR

2. Tubuloglomerular feedback

Myogenic Regulation of GFR

Mean arterial pressure (MAP) increases pressure in afferent (feeding) arteriole → walls stretch → smooth muscles contract in response → increased resistance → reduced blood flow

Tubuloglomerular Feedback

GFR increases → flow through tubule increases, flow past macula densa increases → paracrine from macula densa to afferent arteriole → arteriole constricts, GFR decreases

Renal Exchange Reabsorption

Selective transport of molecules from renal tubules to peritubular capillaries then returned to general circulation. Some reabsorbed completely, others regulated to vary excretion rate, many use active reabsorption

Renal Reabsorption Location

Mainly in proximal and distal convoluted tubules

Peritubular Space

Space between peritubular capillary and renal tubule, filled with interstitial fluid

Barriers for Renal Reabsorption

Tubule epithelial (primary barrier)

Capillary endothelial cell (barrier only for proteins and cells)

Active Renal Solute Reabsorption

Route 1: Active transporter moves solute into tubule epithelial tubule cell → diffuses back into peritubular space, then plasma

Route 2: Diffuses into tubule epithelial cell → actively transported into peritubular space, then plasma → lowers concentration in cell again

Renal Water Reabsorption

As solutes get reabsorbed into plasma, increases osmolarity of plasma, water diffuses down gradient into region of high osmolarity

Passive Renal Solute Reabsorption

Z is passively reabsorbed because it is both more concentrated in tubular fluid and able to permeate tubular and capillary membrane

Transport Maximum

Pumps transporting solutes can get saturated, maximum reached when solute concentration is so high all pumps are occupied

Renal Threshold

Plasma concentration of solute where spillover into urine occurs

Glucose Transport Maximum

Glucose freely filtered at glomerulus, normally 100% actively reabsorbed into blood. If glucose concentration higher than normal (diabetes), pumps saturate and glucose remains in urine.

Diabetes Mellitus

Causes [glucose] in plasma to be elevated (hyperglycemia), glucose appears in urine. Affects osmotic pressure → less water reabsorbed, more thirst in patients. Can also cause diabetic Nephropathy, since high [glucose] damages nephrons

Renal System Secretion

Removes after reabsorption, transport mechanisms + barriers the same but opposite direction. Decreases [solute] in plasma for substances including potassium, hydrogen ions, choline, creatinine, penicillin

Renal Tubule Specialization

Regions of tubules differ by substance transported:

Non-regulated high reabsorption: in proximal tubules. Folded membrane + leaky epithelial junctions

Regulated reabsorption+secretion: in distal tubules and collecting ducts. Tight epithelium + regulation hormones

Excretion Rate of Solute

E = F + S - R

F: filtered load
S: solute secretion
R: reabsorption