kidney receives 25% of cardiac output

Renal Cortex: outised dark red.  gets 90% renal blood, uses 8% O₂ "rich man"

Renal Medulla: inside light.  gets 10% renal blood, uses 80% O₂ "poor man"

1 blood enters Afferent arterioles, 20% filtered

2 blood enters efferent arterioles

3 blood deltas into capilaries to suply renal tubiles

4 blood gathers into veins to leave kidney

happens at renal corpuscle

1 blood enters efferent arterioles.  filtration rate depends on BP

2 capillary filtration

3 basement membrane full of (-)

4 single cell layer epithelial cell filtration.  "podocytes"

filtrates: water, sugar, salt, urea, AA

at proximal tubules

2 methods, Paracellular (across tight junctions.  water/ions follow Na).  Transcellular (through the cell).

Endogenous: body made

exogenous: drugs

excretion=filtration+reabsorption+secretion

PH balance: can lose bicard or H⁺

(kidney usually excretes acids)

Renal fuel

Normal

Acidosis

Fasting

normal: lactate

acidosis: Glutamine

Fasting: Fatty Acids

(the medulla uses glucose made from cortex)

as ph ↓ more glutamine taken up

glucocorticoids result in more glutamine made

<Endocrine function>

Erythropoietin

Renin

Erythropoietin: activated when low O₂, triggers bone to make more RBC

Renin: protein made in, and activated by  granular cells.  renin is the rate limiting step.  

ACE inhibitors

Angiotensin II receptor blockers

ACE inhib: vasoconstrictor "Pril"

Angiotensin II receptor blockers: Sartans

Periportal: more O₂ more mitochondria, oxidative metabolism

Perivenous: less O₂ less mitochondria, anaerobic metabolism

Kupffer Cells: (reticuloendothelial).  macrophage.  blood flow from intestine brings victims.  so bacteria wont enter systemic circulation.

blood enters through

portal vein (70-80%) from GI, high nutrients, low O₂

Hepatic artery (20-30%)

leaves by central Vein

insulin more important than glucagon

glucose levels stable during starvation,

Fatty acids & ketones ↑ during starvation

Periportal: lactic acid-> glucose-> glycogen.  VLDL assembly.  β-oxidation (makes cell ATP)

Perivenous: anaerobic glycolysis.  Glucose from diet-> glycogen.  VLDL assembly.  some fatty acid/TAG Synthesis.  glucose-> lactic acid

Intermediate starvation

4-24 hours

Periportal: gluconeogenesis, glycogen breakdown, VLDL assembly, β-oxidation

Perivenous: anaerobic glycolysis, glycogen breakdown, VLDL assembly, glucose-> lactic acid

liver metabolism

7-40 days

Periportal and perivenous same*

(glucogon is gone)

gluconeogenesis for export

ketone body formation & export

β-oxidation

lots of glycolytic enzymes made

few gluconeogenesis enzymes made

lots of gluconeogenesis enzymes made

lots of aminotransferase (urea cycle enzymes) produced

few fat synthesis enzymes made

Calories/g

Fat

Carbs

Protein

OH

fat: 9

Carbs: 4

Protein: 4

OH: 7

Liver Detox

Phase 1

Phase 2

liver takes in foreign molecules makes them hydrophylic.

Phase 1: detox by cytochrome P450

drugs can induce (more breakdown of other drug), or inhibit (less breakdown of other drug)

Phase 2: detox by enzymes

CFTR: protein that catalizes the movement of Cl^-

effects Na and water too.  results in thick mucous in lungs.

expressed in pancreas, lung, liver, sweat glands

Channel: opened by cAMP cascade.

heterzygotes protected from cholera, because lose less water.

makes Nucleotides

used as fuel

muscle degradation releases glutamine when starved.

Glutaminolysis: glutamine-> alanine+9 ATP.  pathway needs O₂.  uses power of TCA

lose B12 absorption

lactose intolerance

Islets of Langerhans: endocrine function.  insuline β cells.  glucagon α cells.  somatostatin Δ cells

Acinar cells: exocrine function.  pancreatic enzyme & bicarb

big pancreas because too much pancreatic enzyme. 

symptoms: high amylase and lipase, high WBC.

causes: OH, blocked bile duct, CF, side effects.

treatment: analgesics, IV

usually fat soluble enters brain easily exept

usually hydrophylics arent absorbed easily exept

Phenobarbitol and phenytoin arent absorbed as much because they bind to plasma proteins.

Glucose and L-Dopa absorbed because cariers

L system: for large branched AA (L-dopa)

A system: for alanine/glycine/serine (small neut)

ASC system: alanine, serine, cysteine

multy drug resistance,

protein transfers hydrophobic molecules to give synthetic/natural resistance for tumors

in blood brain vessels

"protects brain from neurotoxins"

posterior pituitary

because needs to export products into blood

can use glucose

can use glycogen

can use ketones

can't use fats

deficient in HGPRT

(can't recycle nucleotide bases)

Lesch-Nyham disease

self mutilization

retardation

molecule helps muscle make ATP

creatine phosphate +ADP-> ATP + Creatine

creatine-> creatinine-> urea

creatinine in blood = kidney damage not filtered

ATP/Creatine phosphate

glucose: fast type II

fatty acids: slow type I

Muscle types

type I

Type II A

Type II B

type I: red, high mitochondria, high myoglobin, lipid rich

Type II A: lipid rich, glycogen rich,high aerobic/anaerobic

type II B: white, high glycogen

Lipoprotein Lipas

Alanine

Glutamine (makes 2 urea)

why?:

both cary amino groups to liver to make urea, both can be used by the liver to make glucose,

cyclic, binds metals,

4 pyrole rings linked by methenyl bridges

differ by side chains attached to the 4 pyrole rings

each pyrole can bind 2 side chains.  (IV different arrangements)  only type III asymmetric on ring D is physiologically important

Uroporphyrin

coproporphyrin

Uroporphyrin: acetate & propionate side chains.

coproporphyrin: methyl & propionate side chains

exist as reduced form.  colorless

makes porphyrins

Liver & Bone marrow. step 1,

1 Glycine + Succinyl CoA (intermediate from TCA) by ALA Synthase makes ALA.  Pyridoxal phosphate coenzyme, rate limiting.

2 ALA + ALA by ALA dehydrase make porphobilinogen.

3 4 porphobilinogens condense to make urophyrinogen III

4 urophyrinogen III-> protoporphyrin IX-> Heme

5 Fe added (ferrochelatase speeds up)

Agents that affect Heme Biosynthesis

Hemin

Babituates

Lead

Hemin: inhibits the formation of ALA.  (rate limiting step)  made when too much porphyrin, not enough globin.  Heman causes ↓ synthesis of ALA synthase enzyme

Barbiturates: like phenobarbital cause more Heme production

Lead: inhibits formation of Heme

Porphyrias

Diagnosis

Symptoms

cure

Porphyrias:  enzyme disorder, buildup of intermediates.  most Dominant (erythripoietic porphyria recessive).  problem @ RBC or liver.

Diagnose: buildup of intermediates

Symptom: itch, light sensitivity because makes superoxide O₂ radicals.

Cure: inject hemin

Background info: Biliruben hydrophobic, conjugated biliruben hydrophylic, albunin alone harmful to CNS.

1 Make Biliruben:  NADPH + O₂ break porphyrin ring.  makes Biliverdin.  reduced to Biliruben "Bile pigments".  

2 Uptake of Biliruben by liver: Biliruben insoluble in plasma, so albunin transporter.  Biliruben enters hepatocyte, binds to ligandin.

3 formation of Biliruben diglucuronide: Biliruben + (2)Glucuronic acid= very soluble.  

4 excretion of Biliruben as bile: Biliruben diglucuronide transfered to bile, (unconjugated Biliruben not excreted)

5 Formation of Urobillins in intestine: Biliruben diglucuronide hydrolyzed/reduced by gut bacteria to make Urobilinogen (colorless). some urobilinogen reabsorbed and transferred to kidney to make Urobillins.  Most urobilinogen changed into stercobilin feces excretion 

Jaundice

Hemolytic Jaundice

Obstructive Jaundice

Hepatocellular Jaundice

Newborns

Hemolytic Jaundice: RBC lysis-> high biliruben, more than liver can handle, so unconjugate biliruben in blood.  also high conjugated biliruben released from liver, excreted.  dark yellow urine.

Obstructive Jaundice: plugged bile duct, biliruben cant get to intestine.  Feces.  also if backup enough, liver will release conjugated biliruben into blood.  urine. 

Hepatocelular Jaundice: liver damage.  release conjugated biliruben in blood. Urine.  later, liver less effective, unconjugated biliruben in blood

Newborns: premature. can't conjgate billiruben.  untreated=brain damage. 

• jaundice is the symptom not the disease

• conjugated is water soluble

• unconjugate is not water soluble (if its in blood there is a big problem)
• making ALA is rate limiting step
• breaking hemoglobin goes from hemoglobin-> biliverdin-> Biliruben-> Urobilinogen->Urobillin/stercobillin

<more>

glucagon/EP to counter insulin, breakdown of glycogen,

more glutamine->ATP by intestine,

synthesis and excretion of proteins by liver

less albunin by liver

adipose tissue->fatty acids

protein->AA for gluconeogenesis in liver

patients have hyperglycemia

anaerobic, use cori cycle lactic acid->glucose

aginine->NO

more coagulation

<less>

fatty acid-> ketone body by liver

less Nitrogen balance

opsinization: promote pathogen/phagocyts

promote pathogen cell lysis

prevent autoimmune reactions

WBC trigger proinflamitory cytokines

causes inflamation, so need anti-inflamitorys

good nutrition

give beta blockers, propranalol,

triglycerides in adipose

glycogen in liver

proteins in skeletal muscle

component C3 to help destroy pathogens

coagulation factor fibrinogen

ceruloplasmin to deliver nutrients to wounds

hepatoglobin to bind free hemoglobin at wounds

1 what derivitives of Arginine/Lysine improve muscle performance?

2 Nitroglycerine & Arginine are precursers for?

3 prozac prolongs what neurotransmitter derived from tryptophan?

4 Elavil prolongs the action of what neurotransmitter derived from tyrosine & Phenylaline?

5 to relieve parkinson's disease, L dope is administered with what else?

1 Creatine/Carnitine

2 NO

3 Seratonin

4 NE

5 drugs that inhibit non-neuronal L-dopa metabolism

How does Cholera toxin work?

How does Prozac work?

increases intestinal Seratonin-> activates enteric NS. 

Prozac inhibits reuptake of Seratonin

Made of Niacin and tryptophan

makes NAD

"about 50% of the niacin equivalents in the average diet in the usa are derived from tryptophan".  know because testing by giving niacin different diets

lack of dopamine

solve: give L dopa/DOPA-decarboxylase inhib that doesnt enter brain.

how does L-dopa from tyrosine make melanin

how does L-dopa from tyrosine make Dopamine

tyrosinase

Tyrosine hydroxylase

Thyroid Hormone

T4 and T3

works with Iodine.

relwased in response to TSH

iodine deficiency = goiter