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JAUNDICE Flashcards

1
Q

describe the liver?

A

largest and most important organ

2% of total body weight –> 1.5 kg

Function unit is the liver lobule ( 0.8-2 mm in diameter )

50k to 100k lobules in human liver

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2
Q

describe liver lobule ?

A

Constructed around the central vein which empties into hepatic vein and then IVC

Composed of several liver cellular plates that radiate from the central vein like the spokes of wheel

Each liver plate is two cell Thick

Between the 2 cells –> Bile canaliculi that empty to bile duct

other type of cells around the venous sinusoids :

Typical endothelial cells

Large kupffer cells –> resident macrophages

in the endothelial linings has large pores between the endothelial and hepatic cells are tissue spaces –> SPACE OF DISSE

Million spaces of dissse connect the lymphatic vessels

so when we have excessive fluid , the lymphatic vessels drain it

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3
Q

what are the functions of liver?

A

Blood reservoir —> stored in sinusoids

Blood cleansing

Metabolic function

Bile synthesis

detoxification and excretion

Synthesis of substances used in coagulation

storage of vitamins

Iron buffering and storage

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4
Q

what is the blood supply of liver?

A

Dual blood supply :

Hepatic artery from celiac trunk

Portal vein

27% of the cardiac output

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5
Q

how does the the liver act as blood reservoir ?

A

Expandable vessels act as valuable blood reservoir

Extra blood can be stored in hepatic veins and sinusoid

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6
Q

describe the resistance caused by sinusoid ?

A

Resistance to the blood flow through hepatic sinusoid is low

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7
Q

what does cirrhosis do the resistance?

A

increase the resistance to blood flow

because the pressure difference between portal vein and hepatic vein is low —? portal vein pressure is 9 and hepatic vein is 0 so the total is 9 which is very low

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8
Q

describe the liver reserving blood during cases like cardiac failure ?

A

normal blood volume in it, including that is in both hepatic vein and hepatic sinus is about 450 milliliters

When we have high pressure in the right atrium , it cases backpressure to the veins in the liver

This will cause the liver to expand and 0.5 to 1 liter of blood is stored

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9
Q

what happens in cirrhosis ?

A

liver parenchyma cells are replaced by fibrous tissue

this fibrous tissue will compress the blood vessels , impending the flow of portal blood through liver

Increase the resistance

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10
Q

what causes cirrhosis ?

A

Alcoholism

Excess fat accumulation in liver

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11
Q

how does portal hypertension happen?

A

Large clot that develops in the portal vein or its major branches

When portal system is suddenly blocked the return of blood from intestines and spleen through liver portal blood flow

system to systemic circulation is impeded

this impedance result in portal hypertension

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12
Q

how is the function of blood cleansing is achieved?

A

Hepatic macrophage system

Very efficient phagocytic macrophages in less than 0.01 second the bacterium passes inward kupffer cell , it is digested

Less than 1% of bacteria entering portal blood from intestine , succeed in passing to systemic circulation through liver

Sample of portal blood from portal veins before it enter liver shows colon bacilli when cultured but sample from systemic circulation show growth of colon bacilli is rarely

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13
Q

what are kupffer cells ?

A

macrophages in the liver

Kupffer cells line the hepatic venous sinuses

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14
Q

how is metabolic function achieved?

A

chemically reactant pool of cells with high rate of metabolism

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15
Q

describe the carbohydrate metabolism in the liver?

A

Storage of Glycogen

Conversion of:

Galactose —> glucose
Fructose —> glucose

Gluconeogenesis to maintain normal blood glucose lvl

Formation of chemical compounds from products of carbohydrate metabolism

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15
Q

describe the fat metabolism in the liver?

A

Oxidation of fatty acids ( energy source )

Synthesis of cholesterol/phospholipids/lipoproteins

Synthesis of fats from proteins and carbohydrates

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16
Q

describe protein metabolism in the liver?

A

Deamination of amino acids is required so they can be used for energy converted into carbohydrates of fat

Formation of urea : Removes ammonia from the body fluids

Formation of plasma protein

Interconversion of amino acids

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16
Q

describe the function glucose buffering in the liver?

A

Drop in glucose lvl —> pancrease release glucagon —> breakdown of glycogen —> increase glucose

High glucose lvl —> pancreas release insulin —> stimulates uptake of glucose by cells, glucose stored to glycogen in the liver

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17
Q

describe the storage of vitamins in the liver?

A

Greatest quantities of vitamin A ( 10 month )

Vitamin K

Vitamin D ( 3-4 months )

Vitamin B12 ( at 1 year and perhaps several )

They are fat soluble vitamins

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18
Q

what is the function of vitamin A?

A

Growth

cell division

Reproduction and immunity

most IMPORTANTLY THE VISION

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19
Q

what happens in vitamin A deficiency?

A

in severe vitamin A deficiency night blindness occur because the RETINAL AND RHODOPSIN THAT CAN BE FORMED ARE SEVERELY DEPRESSED in absence of vitamin A so they become low

in vitamin A deficient people the amount of light available at night is little for adequate vision

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20
Q

describe the iron buffer function - apoferritin ferritin system ?

A

The largest quantities of iron are stored in the FORM OF FERRITIN

Hepatic cells contain large amount of APOFERRITIN ( apoferritin + ferrous = Ferritin )

Apoferritin is capable to combine reversibly with iron

Iron extra quantities COMBINES REVERSIBLY WITH APOFERRITIN to form FERRITIN and stored in the liver until its needed

Low level of iron activates FERRITIN to release iron

in the stomach : Mixture of ferrous and ferric is ingested, stomach acid converts ferric to ferrous

Ferrous binds to gastroferritin , transported to small intestine released for absorption by gastroferritin

in plasma ferrous binds to TRANSFERRIN

in liver some transferrin releases ferrous for storage

Ferrous binds to apoferritin to be stored as ferritin ( LIVER STORES FERROUS AS FERRITIN )

Remaining transferrin is distributed to other organs to make hemoglobin and myoglobin

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21
Q

what are coagulation factors formed by the liver?

A

Fibrinogen

Prothrombin

Accelerator globulin

Factor 7 and others

22
Q

what is required for coagulation synthesized?

A

Vitamin K

required for such as prothrombin, factors 7, 9 , 10 , protein C

23
what happens in liver disease ?
Theres decreased production of prothrombin and some other clotting factors due to : 1- poor vitamin K absorption 2- Diseased liver cells cant produce IN absence of vitamin K - blood coagulation impaired can lead to serious bleeding tendencies Vitamin K deficiency seldom occurs
24
how does K deficiency occur ?
Poor absorption of fats from GIT : because vitamin K is fat soluble and ordinarily absorbed into blood along fats Failure of liver cells to secrete bile : inadequate fat digestion and absorption thus vitamin K absorption is decreased
25
describe detoxification and excretion of the liver?
Drug metabolism : sulfonamides, penicillin , ampicillin and erythromycin EXCRETED IN BILE Elimination of ammonia - transforming it to UREA Excretion of hormones : Estrogen , progesterone , thyroxine , cortisol , aldosterone ---> liver damage can lead to excess accumulation of these hormones and overactivity Elimination of bilirubin ---> hemoglobin of red blood cells ---> yellow pigment Calcium excretion - secreted by liver in bile , feces
26
what is the source of ammonia ?
colon Kidneys RBCS metabolism of muscles Deamination process Gut bacterial then absorbed into blood
27
what does ammonia do ?
toxic to brain can cross BBB
28
describe ammonia metabolism by the liver?
Urea cylce in the liver converts ammonia to urea Essentially all urea is synthesized in liver in liver disease ammonia accumulates in blood can cross BBB so extremely toxic to the brain and hepatic coma death Urea is secreted by THE KIDNEY
29
describe whole body ammonia homeostasis is health?
majority of ammonia produced by the body is excreted by the kidneys in the form of urea
30
what is the main function of liver?
Bile secretion 600-1000ml/day
31
what is the function of bile secreted by liver?
Fat digestion and absorption : Emulsification of larger fat ---> minute particles so it is easy for the lipase secreted in pancreatic juice to break it down ( Emulsification (soap function ) breakdown bigger fasts into smaller ones ), Micelles --> micelles formation, bile salts combine with small fats --> can travel and be absorbed Aid in absorption of digested fat --> intestinal mucosal membrane Excretion of waste products from blood : BILIRUBIN AND EXCESSESS CHOLESTEROL
32
where are bile salts synthesized?
in the liver, and are secreted through the bile to the duodenum
33
what is stage 1 of biliary secretion ?
Initial portion is secreted by the HEPATOCYTE Contain : Bile acids , cholesterol, lecithin, bilirubin , ions It is secreted into BILE CANALICULI that originate between hepatic cells
34
describe stage 2 of biliary secretion ?
Bile flow in the canaliculi toward the INTERLOBULAR DUCTS These terminal ducts join together to form progressively larger ducts Finally reaches the HEPATIC DUCTSA AND COMMON BILE DUCTS the Bile has 2 pathways after that : 1-directly to duodenum 2- Diverted through CYSTIC duct into GALLBLADDER
35
What second portion of biliary secretion?
Second portion of watery solution of NA and HCO3 is ADDED TO BILE Secreted by epithelial cells lining THE DUCTS AND DUCTULES This second secretion sometimes increases the total quantity of bile by as much as 100% THIS IS MODIFICAITON TO TO NEUTRALIZE ACIDITY
36
what stimulates the second secretion ?
SECRETIN ( stimulated by PH of chyme and it will reduce chyme acidity and neutralize acidity by HCO3 ) which causes release of additional quantities of bicarbonate ions to supplement the bicarbonate ions in pancreatic secretion this help neutralizing acid that empties into duodenum from the stomach )
37
where is bile stored?
liver cells mostly stored in the gallbladder 12 hours of bile secretion ( about 450 ml ) Can be stored as 30 to 60 ml in the concentrated form
38
why is it stored in concentrated form?
because water , sodium, chloride , most other small electrolytes are continually ABSORBED THROUGH GALLBLADDER MUCOSA
39
what stuff will be concentrated?
Bile salts , cholesterol , lecithin , bilirubin will be concentrated
40
what causes absorption in the gallbladder?
Active transport of sodium through gallbladder epithelium Followed by Secondary absorption of Cl AND WATER and most other diffusible constituents
41
how is Na absorbed ?
reabsorption ( from lumen to the blood ) From the Lumen NA is actively absorbed in exchange for H via Na/H exchanger then actively pumped out to the Interstitial space via Na/K pump ( Na goes out and K come in to the cell ) So: Na from the lumen goes in via Na/H crossing the cell ---> through Na/K pump to the outside ( interstitial fluid ) to be REABSORBED In exchange for the Na you pump in K ---> K doesnt stay inside the cell , leak out and it is pumped inside again ( NOT REABOSRBED JUST PUMPED INSIDE VIA NA/K pump Na is reabsorbed Cl follows Na ---> reabsorbed Water ---> follows NA and Cl both through transcellular and paracellular routes ) --> REABSORBED most ions will BE ABSORBED EXCEPT K K LEVELS REMAIN HIGH AT THE GALLBLADDER
42
what is the CHEMICAL Intestinal control of bile secretion?
Bile salts ( stimulates the liver to increase the production of bile , too much bile acid in diet = increased bile production ) Fat digestion after meal ( if u eat more unprocessed fat ---> more bile stimulated )
43
what is the hormonal control of intestinal phase of bile secretion ?
Secretin ---> stimulates an aqueous alkaline secretion CCK ---> contraction of gallbladder and Relaxation of Sphincter of oddi contraction of gallbladder = squeeze bile to flow out if gallbladder contractions and sphincter not relaxed bile will not secrete efficiently CCK also involved in vagus stimulation which causes weak contraction of gallbladder ( MOST IMPORTANT ONE CCK MOST IMPORTANT
44
what is the neural control of intestinal phase of bile secretion ?
vagus stimulation enteric nervous system MINOR ROLE
45
what causes EMPTYING of gallbladder?
CCK most potent stimulus for causing bladder contraction Digestion in the upper GIT ( FATTY MEALS ) ---> CCK release ---> emptying of chyme Rhythmical contraction of the gallbladder wall Relaxation of the sphincter of ODDI EMPTY INTO DUODENUM
46
what is the other function of CCK?
activates VAGAL afferent triggers VAGOVAGAL reflex --> reinforces gallbladder contraction via ACH and relaxation of sphincter of oddi via NO and VIP
47
what does bile contain ?
Bile salts Bilirubin ( yellow pigment which is end product of hemoglobin degradation ) Water Cholesterol Fatty acids Lecithin Na K Ca Cl HCO3 During the concentration process in gallbladder, water and Large portion of electrolytes EXCEPT CALCIUM AND POTASSIUM WHICH STAYS IN Bile salts, and lipid substances, cholesterol and lecithin are not REABSORBED and are concentrated in the gallbladder bile LESS WATER, NA, CL, HCO3 cuz reabsorbed MORE CA AND K ARE HIGHER IN BILE
48
describe metabolism of RBC ?
Fragile red blood cells rupture their cell membrane Self destruct in the SPLEEN Hemoglobin is released and PHAGOCYTIZED Hemoglobin is broken down into HEME AND GLOBIN Heme will breakdown into iron and protoporphyrin Globin will be broken to amino acid Iron will be stored as ferritin, hemosiderin, etc Protoporphyrin will be converted to bilirubin
49
what happens if spleen is removed?
increased lvl of old abnormal cells
50
what phagocytizes the hemoglobin ?
Kupffer cell in the liver Macrophages in bone marrow and spleen
51
how is bilirubin excreted?
Bilirubin is picked up from the blood by liver ( Secreted into intestine in the bile ) Bilirubin alone is unconjugated form picked up by the liver ---> become conjugated in the liver ---> conversion to urobilinogen in liver ---> from blood becomes urobilin by kidney excreted in urine and INTESTINE CONVERTED STERCOBILIN WHICH IS EXCRETED IN FECES
52
which form of bilirubin is toxic?
the unbound form the unbound is more dangerous than bound
53
describe the toxicity of bilirubin ?
normal physiological condition ---> low bilirubin level less than 1.2 mg increased Free bilirubin can cross the blood brain barrier Binds to phospholipid ( gangliosides ) of neuronal plasma membrane LEADS TO IRREVERSIBLE BRAIN DAMAGE

PHYSIOLOGY-Y2S2 (12 decks)

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