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Physiology Topics
Physiology
Organization: fluid mosaic lipid-protein model (1972 Singer, Nicolson) fits on TD stability
o Semi permeable lipid bilayer (hydrophilic heads outside, lipophilic tails inside) in which membrane proteins are inserted
Chemical composition: 30% H2O, 70% organic substances (proteins + lipids barrier: more lipids; metabolism: more proteins)
Membrane proteins:
o Ensure functionality:
Transporter (e.g. maintaining of ion conc.) carrier proteins, channel proteins
Enzyme (protein synthesis)
adenylate cyclase
guanilate cyclase
phospholipase C
protein kinases A, C
Cell surface receptor (signal transmission, reaction with ligands inducing special reactions inside the cell)
Adrenergic (react to symphatic neurotransmitter noradrenalin)
o Alpha 1 receptors
contraction of smooth muscles of vessels and bronchioles
o Alpha 2 receptors
contraction of smooth muscles of digestive sphincters
o Beta 1 receptors
stimulating effects on heart
o Beta 2 receptors
relaxation of smooth muscles of vessels and bronchioles
Cholinergic (react especially to acetylcholine)
o Nicotinic receptors
stimulated by acetylcholine and nicotine
present at ganglionic synapses, neuromuscular junctions
blocked by curare
o Muscarinic receptors
stimulated by acetylcholine and muscarine (Pilzgift)
present in end-organs (ACh released by postganglionic neurons/parasympathetic)
blocked by atropine
Cell adhesion (interacting/identifying between cells cell identity marker role in immune response)
Attachment to cytoskeleton
o Intrinsic (peripheral) proteins outside of bilayer (on outer or inner surface, often to integral proteins attached)
o Extrinsic (integral) proteins inside of bilayer (can be completely through membrane transmembrane proteins)
Jan Kirchhof
Physiology
Topic 2
Mechanism of transport through cell membrane
Passive transport (no energy consumption, transport with/ down the conc. gradient)
o Simple diffusion
Uncharged particles flow from higher to lower concentrations (speed depends on: permeability, lipid solubility)
lipophilic particles through lipid bilayer, hydrophilic ones through aquaporins
o Facilitated diffusion by carrier proteins
High speeded transport for too large particles (e.g. glucose)
Transmembrane protein transporter/ carrier protein (specific for certain particle)
Can be coupled with other transport (e.g. sodium) cotransport
o Diffusion using channel proteins
Integral membrane proteins (bidirectional)
Ion channels (sodium, potassium, calcium channels)
o Valtage-gated opening depends on electrical gradient
Aquaporins (water channels)
Active transport (energy consumption (ATP), transport against conc. gradient, optimal at 37C)
Primary active transport (direct use of energy (ATP hydrolysis))
Sodium potassium pump (maintains resting potential):
o ATP-ase (membrane protein)
+
intracellular face: binds 3 Na to ATP pumped out
+
extracellular face: binds 2 K to ATP pumped in
+
secondary active transport (use of stored energy in Na conc. gradient)
made by carriers (integral membrane proteins)
uniport transport: single substance in certain direction
cotransport: transport of a substance is coupled with transport of another substance
o symporters: 2 substrates in same direction (e.g. sodium glucose transporter)
o antiporters: 2 substrates in different direction, using conc. gradient of one to drive the other
Vesicular transport (transport of macromolecules):
Exocytosis:
releasing proteins
Endocytosis:
importing proteins by enclosing them in membrane
Phagocytosis (cell eating): immersion of solid substances
pinocytosis (cell drinking): immersion of liquid substances
Jan Kirchhof
Physiology
Topic 3
Membrane potential
resting potential:
o selective permeability of cell membrane:
inside (neg.):
potassium ions, organic anions (macromolecules, cannot pass membrane)
outside (pos.): sodium ions, chloride ions
o ions are asymmetrically distributed causes membrane potential of -70 mV
o many blablablablabla hier muss noch weitergemacht werden (s.28)
Action potential:
o Cell is in resting state and receives a signal (voltage variation)
+
Membrane permeability changes voltage gated Na channels open sodium flows inward inside becomes
positive
If a certain threshold is reached action potential (all or nothing, amplitudes same value, strengthen by frequency)
o Depolarization phase (strong depolarization until +30 mV)
+
All Na channels open
+
+
Na channels start closing, K channels start opening
o Overshoot (amplitude is reached)
o Repolarization phase:
+
K channels opened potassium flows out inside gets back to resting potential
Sodium potassium pump restarts and renews resting potential
o Hyperpolarization (-90 mV):
2+
+
2+
at depolarization Ca gets into cell gets out at repolarization and keeps K channels open until Ca level is low
Sodium potassium pump renews resting potential
o Resting potential is reached (process lasts 1-2 ms)
Potentials can be measured by intracellular microelectrodes (recorded on oscilloscope)
Jan Kirchhof
Physiology
Topic 4
Water content of the body and organs, water compartments, control of water intake
Water content:
o Age:
fetus
100%
baby at birth
80%
adult
70%
elderly person 50%
o organs:
brain
85%
heart
77%
lungs
80%
teeth
10%
liver
73%
bones
22%
kidneys
80%
muscle
73%
skin
71%
blood
79%
o total body water (compartments):
intracellular
30-40%
Extracellular
16-20% (plasma 4%, interstitial 16%)
lymph, fluid around brain, plasma, joint fluid, fluid in stomach + intestines, blood
solid matter
40%
tissue, bone
daily water requirements: 30-40ml/kg/day
o sources (2500ml/day)
water drinking, food, metabolic water
o losses (2500ml/day)
urine, feces, respiration, skin
o pathological losses
bleeding, vomiting, diarrhea
control of water intake: neuro hormonal mechanisms and sensation of thirst
o osmoreceptors thirst center in hypothalamus involved hormones:
ADH (antidiuretic hormone)
reduces water elimination by kidney (at night for not peeing in your pants)
Atrial natriuretic peptide
enhances renal elimination of sodium, sec. of water
Renin-angiotensin aldosterone system reduces renal elimination of sodium and water
Renin from kidney ANG1 ANG2 thirst, production of aldosterone (reduce elimination)
Jan Kirchhof
Physiology
Topic 5
Osmosis and osmotic pressure, causes of edema
Movement of H2O through semi permeable membrane to higher concentrated solution (influenced only by particles number)
Isotonic solution:
equal concentration of solutes (isotonic physiologic solution: 9gNaCl/l)
Hypertonic solution:
higher concentration of solutes cells become wrinkled (H2O out of cell)
Hypotonic solution:
lower concentration of solutes
cells swell, membrane ruptures (H2O into cell)
Osmotic pressure:
o Generated by water movement from low to high conc. the higher the conc. the higher the osmotic pressure
o Physiologic solution: 5500 mmHg, 6.7 atm, 300 mOsm
o Movement of water across capillary wall:
More permeable than cell membrane, impermeable for proteins
depends on balance between hydrostatic pressure and oncotic pressure (osmotic pressure of proteins) gradient
edema:
o accumulation (Anhufung) of fluids in interstitium (swelling of parts of the body, usually legs gravity)
o causes:
reduced concentration of plasma proteins (loss, reduced synthesis (kidney, liver disorders), diet deficiency)
increased capillary permeability (inflammation)
increased venous pressure no balance between pressure gradients (heart failure, standing still)
blocked lymphatics (filarial worms (Fadenwrmer), removal of lymph vessels)
Jan Kirchhof
Physiology
Topic 6
Blood pH, buffers, acidosis, alkalosis
Jan Kirchhof
Physiology
Topic 7
Blood volume, hematocrit, control of blood volume
Blood volume:
2
o 5-6 liter (depends on body volume and gender 76 ml/kg, 2.6 liter/m )
o Composition:
Plasma (55%)
Cells (45%)
White blood cells and platelets (<1%)
Jan Kirchhof
Physiology
Topic 8
Plasma electrolytes, their roles, anion gap
Jan Kirchhof
Physiology
Topic 9
Plasma proteins: classification, roles
Plasma proteins (6-8 g/dl blood; synthesis of 15 g/day in liver): albumin, globulin (alpha, beta, gamma), fibrinogen, hormones, enzymes
o Seperation by electrophoresis (alkaline solution proteins become neg. charged go to pos. pole (in order mentioned above))
Albumin:
o Molecular mass: 67 kDa
o Most abundant (hufigestes) >55%
o Produced in liver
o Maintains oncotic pressure
o Transports: hormones, fatty acids, bilirubin, drugs
2+
o Binds Ca
o Buffers pH
Globulins:
o Molecular mass: 90-1300 kDa
o Produced in liver and immune system
o Isolated by electrophoresis in: alpha 1, alpha 2, beta 1, beta 2, gamma
o Transport substances
o Enzymatic active
o Defensive role (immunoglobulins)
Classification due to carried substances
o Metalloproteins (carrying metals):
transferin (Fe), ceruloplasmin (Cu)
o Glycoproteins (carrying carbohydrates):
immunoglobulins (IgA, IgG, IgM,IgE)
o Lipoproteins (carrying lipids):
chylomicrons, VLDL, IDLP, LDL, HDL (due to density)
Roles of plasma proteins:
o Maintenance of oncotic pressure (albumin)
o Maintenance of pH (albumin)
o Transport (espec. by globulins: ions, carbohydrates, lipids, hormones, drugs)
o Defence (globulins: immunoglobulins, complement, properdin, reactive C protein)
o Maintenance erythrocyte sedimentation rate
o Enzymes (activation and inhibition of proteolysis (Proteinabbau), blood coagulation, fibrinolysis (Gerinnselauflsung))
Jan Kirchhof
Physiology
Topic 10
Blood sugars
10
Jan Kirchhof
Physiology
Topic 11
Blood fats
11
Jan Kirchhof
Physiology
Topic 12
Erythropoiesis, erythropoietin, role of iron
12
Jan Kirchhof
Physiology
Topic 13
Characteristics of erythrocytes: dimension, number, composition, lifespan
Dimension:
o Disc diameter: 7 m
o Thickness:
2 m
3
o Volume:
85 m
2
o Surface:
125 m
2
o Total surface: 3000 m
Number of erythrocytes:
12
o 4-6*10 /liter (physiological variations due to age (greater in newborn), sex (greater in males), altitude
Reduced number:
characteristic of anemia
Increased number:
poliglugolia
Different size and shape: category of anemia
Anisocytosis size: <7 m or >10 m
Poikilocytosis shape
Modifications can be observed with microscopes
Properties:
o Highly deformable visco elastic property of membrane important for circulation in small vessels
Composition:
o H2O:
57%
-12
o Hb:
33% (30 pg or 30*10 g)
o Lipids: 7%
o Sugar: 3%
Enzymes playing a role in erythrocytes metabolic activity:
o Carbonic anhydrase
CO2 transport
o 2,3-Diphosphoglycerate binds to tensed form of Hb lowers O2 affinity (O2 is emitted at higher partial pressures of CO2)
Lifespan:
o 120 days (youthful erythrocytes called: reticulocytes (0.5 1.5 %))
o 1% destroyed per day by agglutination and hemolysis
80% in spleen
13
Jan Kirchhof
Physiology
Topic 14
Blood groups: AB0 system, Rhesus system
14
Jan Kirchhof
Physiology
Topic 15
Hemoglobin: quantity, structure, disorders
Hb is red colored protein, made by heme (synthesized in mitochondria) and globin (synthesized in ribosomes)
o Globin: 4 polypeptide chains (alpha, beta, gamma, delta)
3 types of Hb due to the polypeptide chains:
A1
2 alpha + 2 beta
dominant Hb at age of one year
A2
2 alpha + 2 delta
F
2 alpha + 2 gamma
fetal Hb
o Heme (4): tetrapyloric structure, porphyrine ring, contains iron, can bind one O2 molecule
8
Each erythrocyte contains 3*10 Hb molecules (88% of erythrocyte)
Total amount of Hb in blood:
o Men
13.5 16.5 g/dl
o Women
12 15 g/dl
o Children
11 16 g/dl
o Pregnant women
11 12 g/dl (some amount of Hb, but more volume)
o 1 g Hb can combine with 1.34 ml O2 1 liter blood can carry 2 dl O2 (5 liter blood = 1 liter O2)
Hemoglobin disorders (modification of structure, shape, capacity to carry oxygen) hemoglobinopaties:
o Thalasemia (recessive hereditary disease):
Deficiency in globin chain production: no or less production of beta chains
no HbA1, instead HbA2, HbF instability of erythrocytes quick destruction inefficient erythropoiesis
chronic anemia
especially in mediterranean zone
o Sickle cell disease:
Abnormal structure of globin chain (beta6 glutamine is exchanged with valine) forming HbS (sickle)
erythrocytes are sickle shaped, have reduced resistance more hemolysis (excreted in urine red color)
multiple organ infarcts (thrombosis)
Red blood cell destruction (in spleen, liver, bone marrow rupturing of cell membrane):
o Hb is degraded to:
Globin recycled
Heme is degraded to:
Iron recycled
Biliverdin is reduced to:
o Bilirubin is bound to albumin
o forming complex albumin-unconjugated/indirect bilirubin
o goes to liver where complex is broken
o bilirubin is recombined with glucoronic acid
o forming conjugated/direct bilirubin
o excreted in bile going to small intestine, transformed to:
Stercobilinogen and stercobilin
partially excreted (color of stool)
partially reabsorbed (excreted by kidney)
Urobilinogen and urobiln (color of urine)
o Total amount of bilirubin in blood: 0.8 mg/dl
o VN (bilirubin in blood) = 0.2 1.0 mg/dl
> 2 mg/dl icterus/jaundice (yellow colored skin and conjunctiva (Bindehaut))
excessive hemolysis (increased bilirubin production over livers capacity)
prehepatic
hepatic disease (decreased bilirubin uptake by the liver)
hepatic
obstacles on bilary truct (white stool operate quick)
posthepatic
15
Jan Kirchhof
Physiology
Topic 16
Compounds of hemoglobin
oxyhemoglobin
O2Hb
o labile combination Hb and oxygen major form of oxygen transport in arterial blood
o each Hb can bind 4 O2 molecules
reduced Hemoglobin
HHb
+
o deoxyHb: O2Hb HHb + O2 + K
o present in venous blood (3 g/dl, if amount increases to 4-5 g/dl cyanosis (bluish lips and fingers))
carbaminohemoglobin CO2Hb
o labile combination Hb and carbondioxide form of CO2 transport in the blood
carboxyhemoglobin
COHb
o stable combination of Hb and CO (great affinity of Hb to CO)
o VN (COHb/Hb) < 1% (levels of city people and smokers are higher, appr. 5%)
10% impaired judgement
50% unconsciousness (risk of death)
CO poisoning: reddish skin
o Withdraw CO from Hb with high partial pressure of O2 (increases O2 affinity)
methemoglobin
MetHb
2+
3+
o Fe Fe (oxidation): cannot bind to oxygen
o VN (MetHb/Hb) = 0 3%
higher values lead to cyanosis (can be caused by nitrates from water)
dangerous for babies, they do not have MetHb reductase
sulfhemoglobin
SHb
o stable combination of Hb and sulfur
o no carriage of oxygen
o occurs when Hb is exposed to some drugs (phenacetin, sulfonamides)
relationship of Hb binding O2
o arterial blood: ca. 20 ml O2 / 100 ml blood (98% saturation, because some venous blood)
o factors increasing Hb affinity binding O2 (at lungs):
low temperature (in lungs)
weak basic pH, low pCO2 Bohr effect
o factors decreasing Hb affinity binding O2 (in tissues):
high temperature (in tissues)
weak acidic pH, high pCO2 Bohr effect
2,3 DPG (tensed state of Hb takes 2,3 DPG stabilizes T form, O2 emission)
16
Jan Kirchhof
Physiology
Topic 17
Leucocytes: number, classification, leucocytic formula
17
Jan Kirchhof
Physiology
Topic 18
Lymphocytes B and T, classification, roles
Both types are produced in bone marrow, distinguishable by specific markers (CD)
T-cells (matured in thymus (T), recognize antigens in antigen presenting cells):
o T helper/inducer cells (CD4 marker)
stimulate activity of B-cells, cytotoxic T-cells, suppressor cells
o T amplifier (verstrken) cells (CD4 marker)
stimulate activity of cytotoxic T-cells, natural killer T-cells
o T suppressor (unterdrcken) cells (CD5 marker)
reduce activity of killer T-cells
o T cytotoxic/killer cells (CD8 marker)
can kill all foreign recognized cells (cancer, virus infected, transplanted)
secrete: perforins, tumor necrose factor, interferons
o T natural killer cells
front line soldier kill directly any non-self cell without B-/T-cell action
B-cells (matured in bone marrow (B))
o Stimulus: transformed in plasmocytes
they secrete antibodies/immunoglobins react with specific antigens
18
Jan Kirchhof
Physiology
Topic 19
Substances involved in the nonspecific body defense
non specific body defense belongs to the second line immediate response involving:
o phagocytes (neutrophils, eosinophils, basophils, monocytes-macrophages (big eaters)
o proteins:
interferons (alpha, beta, gamma)
produced when cell is infected by virus
protect other cells around
resistance is short termed (one week)
complement proteins (have to be activated)
produced by liver
coat surface of microbe (opsonization) facilitate identifying + engulfing (verschlingen) for macrophage
membrane attack complex (MAC) form holes in microbes cell membrane death of microbe
properidin
act with activated complement proteins on microbes, fungi destroying them
lisozyme
present in saliva and tears
destroys cell membrane of bacteria
reactive C protein (globulin)
activates complement proteins
facilitates opsonization and phagocytosis
19
Jan Kirchhof
Physiology
Topic 20
Phagocytosis and inflammatory response
20
Jan Kirchhof
Physiology
Topic 21
Types of immunity, MHC
21
Jan Kirchhof
Physiology
Topic 22
The humoral immune response and cellular immune response
22
Jan Kirchhof
Physiology
Topic 23
Thrombocytes/Platelets: number, morphological characteristics, functions, disorders
Thrombocytes (platelets):
o anucleated (kernlos)
o disc shaped fragements, 2 3 m diameter
3
o VN = 150000 300000 / mm
o Lifespan: 8 10 days
o thrombopoiesis (formation) in bone marrow
hemocytoblast (stem cell)
megakaryoblast promegakaryocyte megakaryocyte platelets (approximately 8000 per megakaryocyte)
o components:
canalicular system
alpha granule (contain Willebrand Factor (vWF), thrombin, thrombospondin, growth factors)
microtubules
glycogen
mitochondria
2+
dense body (contain ADP, Ca , serotonin)
microfilaments
surface glycoproteins (receptors for collagen, ADP, serotonin, vWF)
o function:
scanning vascular system, respond to endothelial damage
bind to injuries (in seconds) component of clotting system
platelet activation (when binding to injuries):
o Exocytosis of dense granules and alpha granules
o Activation of phospholipase A2 (membrane enzyme) formation of thromboxane A2 (TXA2)
o Shape change (projecting fingers)
reversible
o Adhesion between platelets and collagen under endothelium forming platelet plug (white clot)
Supported by receptors (vWF, fibrinogen)
Fibrin strengthens structure platelet aggregation (thrombus formation, growth)
irreversible
o Coagulation reaction is promoted platelet activation + coagulation red clot
o Disorders:
Atherosclerosis
2+
Building up of deposits (fatty substances, cholesterol, waste, Ca , etc.) in inner lining of artery
o Creates plaque
o Reduces blood flow
Activated platelets are involved at damage of endothelial lining and atherosclerotic lesion
o interacting with monocytes, lymphocytes
o Influence plaque progression blood clots blockade heart, brain damage
Causes of arterial wall damage: high cholesterol, smoking, hypertony, DM, obesity, inactivity
Antiplatelet agents can prevent arterial wall damage
Disorder of platelet quantity or quality spontaneous bleedings
Thrombocytopenia (reduced quantity) blood seeps in tissue purpura (purple blotches (blaue Flecken))
Glanzmanns thrombasthenia (hereditary): poor quality, disorder in GP IIb/IIIa (receptor) production
o excessive bleeding
23
Jan Kirchhof
Physiology
Topic 24
Hemostasis: phases, disorders
24
Jan Kirchhof
Physiology
Topic 25
Coagulation of blood, clotting factors, anticoagulants
Coagulation:
o Enzymatic process: fibrinogen is transformed in fibrin that forms a mesh entrapping the blood cells (red thrombus)
Controlled by intervention of clotting factors:
o Factor I
fibrinogen
o Factor II
prothrombin
o Factor III
tissue thromboplsatin
o Factor IV
calcium ions
o Factor V
labile factor
o Factor VII
stable factor
o Factor VIII
antihemophilic factor
o Factor IX
Christmas factor/plasma thromboplastin component (PTC)
o Factor X
Stuart-Prower factor
o Factor XI
plasma thromboplastin antecedent (PTA)
o Factor XII
Hageman factor
o Factor XIII
fibrin stabilizing factor
Most of them are glycoproteins (globulins) formed in liver
Factor II, VII, IX, X need vitamin K for synthesis
o Coagulation cascade:
Initiated by 2 pathways:
Contact activation pathway /small endothelial damage (intrinsic)
Tissue factor pathway / tissue damage (extrinsic)
both activate final common pathway of factor X, thrombin (most imp. subst. of cascade feedback mech.), fibrin
pathways are series of reactins where enzymes + cofactors are activated and catalyze next reaction
learn picture of the book 2 pages after clotting factors
o anticoagulants (inhibit coagulation)
natural anticoagulants:
heparin
o produced in liver and lung (from basophils and mastocytes)
o inhibits activity of thrombin
o acts fast but not long for acute problem
antithrombin III
o inhibits activated II, IX, X, XI, XII, kallicrein, plasmin, VII
o heparin amplifies action
Protein C + S
o Produced in liver with VitK
o Inhibits activated V, VIII
o Facilitates intravasacular clot lysis
Extrinsic anticoagulants:
Coumadin (inhibits vitK no synthesis of II, VII, IX, X)
2+
Citrates (binds Ca )
Hirudin (blocking thrombin)
25
Jan Kirchhof
Physiology
Topic 26
Kidney anatomy, component of the nephron
Kidney:
o Primary organ of homeostasis (Aufrechterhaltung des Gleichgewichts) of:
Volume of body fluids
Composition of body fluids
Excretion of metabolic waste in the urine
o Anatomy:
Large, bean shaped organ, situated at dorsal side of visceral cavity, protected by renal capsule (tough fibrous coat)
Urinary system (way of urine): kidney ureter urinary bladder urethra outside
Components (longitudinal section):
Cortex (low b)
surrounds pyramids (darker, triangular structures)
Medulla (high b)
made by pyramids
Renal pelvis (inner part of kidney)
collects urine from calyces drains in ureter
6
Nephron: basic functional unit of kidney (approximately 10 in kidney, 90% have to work for proper function)
o Glomerulus + Bowmans capsule form renal corpuscle
(situated in cortex continued by)
o Proximal convoluted tubule
(situated in cortex continued by)
o Loop of Henle (u-shaped)
(sit. in cortex or medulla, depends on length continued by)
loop in medulla: juxtamedullary nephron (15%)
loop in cortex: cortical nephron
o Distal convoluted tubule
(situated in cortex continued by)
o Collecting tubule
(goes in medulla continued by ureter)
26
Jan Kirchhof
Physiology
Topic 27
Renal blood flow, pressures
Blood supply:
o Renal artery
Receive approximately 20% of cardiac output (ca. 4 ml/min/g) one of highest blood flow values
o Renal veins drain blood of kidney in vena cava inferior
o Pressures: (values are inaccurate; HP in mmHg (hydrostatic pressure); b in mmHg (oncotic pressure))
Arteria renalis
HP 100
b 30
Afferent arteriole
HP 100-60
b 30
Glomerular capillary
HP 60
b 30-35
Efferent arteriole
HP 60-25
b 35
meeting point of two curves
Peritubular capillary
HP 25
b 35-30
Infrarenal vein
HP 25-10
b 30
Vena renalis
HP 10-5
b 30
Afferent + efferent arterioles are major resistence sites major sites for RBF (renal blood flow) control
If HP > b
filtration (glomerular capillaries)
If b > HP
reabsorbtion (peritubular capillaries)
27
Jan Kirchhof
Physiology
Topic 28
Mechanisms of urine formation
mechanisms:
o Glomerular filtration (blood plasma)
at glomerulus
from vessels to renal interstitial fluid (primary urine)
o Tubular reabsorbtion of water and solutes
at prox. conv. tubules
from renal interstitial fluid to vessels
o Tubular secretion
at distal conv. tubules
from vessels to interstitial fluids
Nephrons receive blood by afferent arterioles entering glomerulus
Blood leaves glomerulus by efferent arterioles
o High vascular resistance low pressure in peritubular capillaries reabsorbtion (H2O and solutes from renal interstitial fluid)
o 90 95% of postglomerular RBF: perfuses renal cortex
o 5 10% of postglomerular RBF: perfuses renal medulla vasa recta
o 1% of postglomerular RBF:
perfuses inner medulla that serves medullary osmolar gradient
28
Jan Kirchhof
Physiology
Topic 29
Glomerular filtration, concept of clearance
Glomerulus is surrounded by Bowmans capsule presents capillaries inside (podocytes around cytoplasmic extension for filtration
Capillaries are very permeable to plasma large portion filtered from blood
o Proteins are not filtered, too big (>10m), if: damage, proteinuria, glomerulopathy
Amount of filtered plasma depends on:
Capillary hydrostatic pressure
55 mmHg
Blood oncotic/ colloid osmotic pressure
-30 mm Hg
Capsular hydrostatic pressure
-15 mmHg
Capsular oncotic/ colloid osmotic pressure
0 mmHg
o +10mmHg towards outside
RBF (renal blood flow):
1250 ml/min
RPF (renal plasma flow):
650 ml/min
GFR (Glomerular filtration rate): 125 ml/min (10/55 * 650 ml)
Resistance of afferent and efferent arterioles important for RBF, RPF, GFR
o Constriction of afferent arteriole
high afferent resistance
lower pressure in glomerular capillaries (lower filtration pressure)
o lower GFR
o Constriction of efferent arteriole
opposite effects
RBF/GFR regulation (autoregulation, nervous regulation, humoral regulation)
o Autoregulation:
Can maintains RBF, GFR in blood pressures between 80 200 mmHg (in absence of neural/humoral factors)
Starts through myogenic response
Outside of 80 200 mmHg more pressure dependent less than 40 mmHg severely reduced GFR
o Sympathetic nerves:
Acts on afferent and efferent arterioles effects RBF/GFR
Cardiovascular baroreceptors effects RBF/GFR
o Humoral regulation:
Hormones for vasoconstriction: noradrenalin, adrenalin, angiotensin, ADH, serotonin
Hormones for vasodilation: prostaglandins, bradykinin, dopamine (!), natriuretic peptide, papaverine)
29
Jan Kirchhof
Physiology
Topic 30
Juxtoglomerular apparatus (JGA) structure and function
JGA is situated near glomerulus and distal tubule (with macula densa)
Equilibrium between GFR and tubular function tubular function is adapted to maintain GFR constant
o tubularglomerular feedback mechanism (TGF)
JGA regulates RBF/GFR through TGF
If GFR changes (e.g. high GFR high tubular fluid flow rate high Cl delivery)
o tubular fluid flow rate changes (through prox. tubule, loop of Henle, dist. tubule (macula densa))
Cl delivery and reabsorbtion rate at macula densa changes
JGA determines vascular volume change by change of:
o Arterial pressure (direct + arterial barareceptors)
o Venous volume (indirect through atrial receptors (Vorhof) sympathetic nerv. sign.; catecholamine (hormons))
o Fluid delivery to macula densa (direct)
JGA response:
o Renin release
changes rate of excretion: H2O + salt; changes peripheral resistance
o GFR change
changes rate of excretion: H2O + salt
o Peritubular capillary pressure change (HP and )
changes rate of excretion: H2O + salt
30
Jan Kirchhof
Physiology
Topic 31
Function of renal tubules
Filtration
o Large portion of plasma is filtered from blood into renal tubules glomerular filtrate
o Needed substances are put back into blood reabsorbtion
o Rest is left and excreted by urine
Reabsorbtion
o Movement of H2O (passive) + solute (active or passive due to substance and tubular segment)
from tubular lumen into peritubular capillary network
Secretion
o solute (mostly active) from blood into tubular lumen
proximal renal tubules
constitution:
o inner surface: luminal surface of epithelium brush border of microvilli (increases surface)
role of epithelium: reabsorb ions, nutrients, H2O transport it to capillaries
o outer surface: basal/lateral cell membrane infoldings, contact with interstitial fluid and blood vessels
+
major function: Na reabsorbtion (60 70% of filtrate)
o at basolateral membrane:
+
+
31
Jan Kirchhof
Physiology
Topic 32
Role of loop of Henle (in medulla)
32
Jan Kirchhof
Physiology
Topic 33
Role of distal tubule
Reabsorbtion of electrolytes and H2O (quantity due to hormonal control by aldosterone and ADH)
Distal tubule can be divided (anatomically + functionally) in 2 parts:
o Cortical collecting tubule (action of aldosterone), 2 cell types
P(principal) cells
+
Secrete K
+
Reabsorb Na
+
aldosterone released at low Na conc. in blood, at dehydration
+ +
+
+
o stimulates Na -K ATP-ase, high number of Na -, K -channels)
o Renin angiotensin aldosterone system (active at hypovolemia, hypotension)
I(interrelated) cells
+ +
+
+
Acid-base regulation (by K -H ATP-ase pump secr. of K , reabs. of H )
o Medullary collecting tubule (action of ADH)
H2O leaves from filtrate to hypertonic medullary interstitium (H2O conservation, reduced diuresis (renal elimination))
ADH mechanism:
ADH attaches to V2 receptor
o Starts cascade (Gs protein adenylate cyclase, cAMP, protein kinase A)
forces insertion of aquaporin2 at laminal surface/apical membrane
H2O moves (due to osmotic pressure) in cells, leaves at basolateral membrane by aquaporin3/4
Kidney is able to maintain osmolality of body fluids constant wide range of osmolar conc. (50 1200 mOsm/l) excretion
33
Jan Kirchhof
Physiology
Topic 34
Urinary concentration and dilution (bad topic)
34
Jan Kirchhof
Physiology
Topic 35
Role of kidney in acid base balance
35
Jan Kirchhof
Physiology
Topic 36
Dieresis, diuretics, composition of urine
36
Jan Kirchhof
Physiology
Topic 37
Renal failure, artificial kidney
37
Jan Kirchhof
Physiology
Topic 38
Micturition (Urinieren)
38
Jan Kirchhof
Physiology
Topic 39
The role of the kidney as endocrine organ
39
Jan Kirchhof
Physiology
Topic 40
The neuro-humoral control of renal function
neural control of renal activity is limited (even normal function of transplanted kidney):
o adrenergic stimulation (by sympathetic splachnic nerves)
+
vasoconstriction (especially at afferent arteriole reduced GFR, increased Na reabsorption at prox. tubule)
Humoral control of renal activity by several hormones:
o ANG2
Via AT1 receptors (ANG2 receptor type 1) vasoconstriction with reduced diuresis
Via AT2 receptors (ANG2 receptor type 2) vasodilatation with enhanced diuresis and natriuresis
o Aldosterone
+
Enhances Na reabsorption
o ADH
Induces massive reabsorption of H2O
o PTH
2+
2+
Reduces loss of Ca , Mg
+
+
Increase elimination of Na , K , HCO3
o Kalicrein-bradykinin system
Induces vasodilatation
Opposing action of renin-ANG system
o Renal prostaglandins (PGE2, PGF1A, PGF2)
Induce vasodilatation with diuresis and natriuresis
o Thyroid hormones
Increase GFR
o Insulin
Influences glucose transport
o ACTH and glucocorticoids
+
Increase glucose, Na reabsorption
40
Jan Kirchhof
Physiology
Clearance: volume of plasma, cleared from a given substance per time unit
o The effect of increasing plasma conc. of a substance according to the clearance depends on handling the substance by tubules
Handling: filtered
clearance is constant
Handling: filtered + reabsorbed
clearance increases
Handling: filtered + secreted
clearance decreases
o With clearance you can determine GFR
Inulin (fructose polymer)
it is only filtered
GFR = (U*V)/P (U: conc. urin, P: conc. plasma, V: volume urin)
Creatinine (endogenous substance)
filtered + 10% secreted (prox. tubules)
o With clearance you can determine RPF
PAH (p-aminohippuric acid (weak acid))
filtered + secreted (renal venous conc. ca. 0)
Renal extraction of PAH ca. 90% represents volume of RPF
o Glucose clearance:
Glycaemia <250 mg/dl
100% of filtrate is reabsorbed
Glycaemia 250 375 mg/dl
reabsorbtion decreases
Glycaemia >375 mg/dl
0% of filtrate is reabsorbed
Glycaemia >250 mg /dl
excretion in urine starts
Clearance: 0 (glyc. 0 250 mg/dl), like inulin (glyc. > 250 mg/dl)
41