MET2 Revision1 Flashcards
What is the CT like in liver?
- Very little
- Sinusoids are supported by collagen type III
Liver lobule structure:
What are the 3 zones in a liver lobule? [3]
Where are the 3 zones located in relation ot the portal triAd?
Differences in appearance between the 3 zones? [3]
Liver lobule structure:
All have different metabolic activities
What are the 3 zones in a liver lobule? [3]
* Zone 1: oxygenated blood
* Zone 2: medium oxygenated blood
* Zone 3: less oxygenated blood
Where are the 3 zones located in relation ot the portal triAd?
Zone 1: closest to portal triad: lighter purple
Zone 3: futhest to portal triad: deeper purple
What are the different functions of zone 1 c.f. zone 3 hepatocytes?
Zone 1 = oxidative/phase II reactions, gluconeogenesis and glycogen synthesis and, proteosynthesis and bile salt formation
Zone 3 = anaerobic/phase I reactions, glycogen stores (glycolysis), fat stores (lipolysis) and pigment store and glutamine synthesis
Describe how blood reaches the central vein
Blood from hepatic artery and portal vein mix and flow toward central vein through sinusoids
What is the name of the resident macrophages in the liver? [1]
Where exactly do they live? [1]
What is the name of the resident macrophages in the liver? [1]
Kupffer cells
Where exactly do they live? [1]
Lumen of sinusoids
The gap between the endothelium and the hepatocytes is called WHAT? [1]
The gap between the endothelium and the hepatocytes = space of Disse
Hepatocytes secrete bile into WHAT? [1]
Hepatocytes secrete bile into canaliculi
Describe the passage of bile into gallbladder
- Hepatocytes secrete bile into canaliculi
- The canaliculi are defined by tight junctions between adjacent hepatocytes
- Bile flows through these narrow tubes towards the hepatic (bile) duct
- From the bile duct it flows into the biliary tree out of the liver to the gallbladder or intestines
Describe the structure of gallbladder cells
Characteristic features:
* Irregular shaped villi
* Lined with very tall columnar epithelial cells
* Smooth muscle in the wall contracts under influence of hormone cholecystokinin
* Expels bile into duodenum
Smooth muscle in the gall bladder wall contracts under influence of which hormone? [1]
Where is it secreted from? [1]
Smooth muscle in the gall bladder wall contracts under influence of hormone cholecystokinin: from duodenum
Which pro-inflam makers are produced when cirrhosis occurs? [3]
Chronic inflammation (TNF alpha, TGF beta, IL1 from Kupffer cells, endothelial cells, bile duct cells and hepatocytes)
Describe the histopathological changes that occur from steatosis (fatty liver disease)
Steatosis is the pathological retention of lipid in hepatocytes
Lipids accumulate in lipid droplets that can eventually displace the nucleus of hepatocytes
Explain how alcoholism can induce steatosis?
Alcoholism can also induce steatosis because the metabolism of ethanol produces NADH which shifts the metabolism of hepatocytes toward lipid synthesis
- Hepatocyte swelling and necrosis
- If chronic then fibrosis
Describe the histopathological changes that occur from cholestasis and why they occur [2]
Cholestasis is a pathological accumulation of bile within the liver parenchyma
It results from blockage of bile ducts or defects in bile secretion by hepatocytes
In this image, note the presence of bile in the ducts and cytoplasm of cells
What are cholelithiasis? [1]
Gall stones
What are cholelithiasis / gall stones made from:
- 80% of time
- 20% of time
What are cholelithiasis / gall stones made from:
- 80% of time: cholesterol stones
- 20% of time: pigment stones: bilirubin calcium salts
Explain the MoA of insulin secretion from B cells
Glucose enters the β-cells
Glucokinase acts as the glucose sensor
Increased ATP/ADP ratio closes the ATP-sensitive potassium channel leading to depolarisation of the plasma membrane
This opens the voltage-gated calcium channel. The increase of intracellular calcium triggers secretion of insulin-containing granules
Name other signals that can potentiate the insulin other than last slide [6]
- Intracellular catobolsim of amino acids increases cellular ATP / ADP ratio (leucine, arginine)
- Fatty acids
- Glucagon like peptide 1 (GLP-1)
- Glucose-dependent insulinotropic
peptide (GIP) - PNS release of Ach
- CCK
(most require glucose for activation)
What is glucagon secretion stimulated by? [3]
What is glucagon secretion inhibited by? [5]
Stimulated:
* Low blood glucose conc
* Increased blood A.A (especially alanine and arginine)
* Exercise
Inhibited:
* Hyperglycaemia
* GLP-1
* Somatostatin
* Insulin
* Zinc
Explain MoA of glucagon working
- Which type of receptor does it bind to?
- Glucagon receptor is a GPCR
- Upon ligand bonding, GTP displaces GDP on the a subunit. A subunit binds to the adenyly cyclase protein to activate
- Causes activation of Adenyly Cyclase pathway
(pathway is a key signalling cascade activated by glucagon). - Causes synthesis of cAMP as a second messenger (v important!) which actiavtes protein kinase A causes phosphorylation of enzymes used for reactions to make glucose
How does insulin switch off glucagon dependent signaliing?
Phosphodiesterase
Effect of glucagon on [4]
glycogenlysis
glycogensis
At the liver: gluconeogenesis
glycolysis
Glucagon increases glycogenolysis
Glucagon inhibits glycogenesis
AND
At the liver: Inhibits glycolysis and increases GNG
What is the effect of glucagon on precursors for GNG?
COME BACK
Glucagon increases amino acids, lactate, and glycerol intake by hepatic cells
Role of catecholamines (in particular adrenaline) with regards to hypoglycaemia
Fight or flight x
E.g. Adrenaline:
It also acts as an insulin counter-regulatory hormone in response to hypoglycaemia
It signals via a G protein-coupled receptor: produces cAMP and causes activation of PKA
Catecholamines monoamines (Dopamine, norepinephrine, and epinephrine) are synthesised from which two molecules? [2]
Where? [1]
Adrenaline synthesised from Phenylalanine and Tyrosine
At: chromaffin cells of the adrenal medulla
Effect of cortisol in:
a) the liver [2]
b) the muscle [2]
c) adipocytes [2]
(opposite of insulin; similar to glucagon)
In the liver:
* enhances gluconeogenesis
* inhibits glycogen synthesis
In muscle:
* inhibits glucose uptake/utilisation
* stimulates protein degradation
In adipocytes:
* it stimulates lipolysis
* Rapid mobilisation of glucogenic amino acids and glycerol/fatty acids from cellular stores
Growth hormone is stimulated by the release of which hormone? [1]
Growth hormone is inhibited by the release of which hormone? [1]
Growth hormone:
- stimulated by growth hormone-releasing hormone (GHRH)
- inhibited by somatostatin (SSTN)
What are the metabolic effects of growth hormone at:
a) liver [2]
b) sk. muscle
c) adipose tissue
What are the metabolic effects of growth hormone at:
a) adipose tissue:
* reduces lipogenesis
* Increases lipolysis
* Overall effect: reduces body fat mass
b) sk. muscle
* Reduces glucose uptake
* Increases b oxidation
c) liver:
* increases production and uptake of IDL, LDL and HDL
What is the effect of growth hormone on IGF-1?
What is the effect of IGF=1 activated? [2]
IGF1 = Insulin-like growth factor 1
GH is a regulator of IGF1, specifically it decreases renal GNG and increases glucose transport
Thyroid hormone release causes increased basal metabolic rate. Explain how [3]
Increase in the number and
activity of mitochondria
* Increases the rate of ATP synthesis
Stimulation of carbohydrate metabolism
* Rapid glucose uptake
* Enhanced glycolysis and gluconeogenesis
* Increased insulin secretion
Stimulation of fat metabolism
* Lipids mobilised rapidly from fat tissue
* Increased fatty acids concentration in the plasma
What are incretins?
Name an important one
Incretinsare a group ofgastrointestinal hormones
GLP-1 (glucaon like peptide)
Effect of glucagon on fatty acid Beta oxidation and de novo lipogensis [2]
Glucagon increases fatty acids
β oxidation
Glucagon inhibits de novo lipogenesis
Growth hormone acts by activating which two receptors?
GH acts via Growth Hormone receptor [1] and Prolactin receptor [1]
Growth Hormone receptor is what type of specific receptor? [1]
GHR is a type I cytokine receptor that lacks intrinsic kinase activity and requires recruitment of Tyrosine kinases to signal
Which part is AP and PP? [2]
The anterior part is derived from an upgrowth from the oral ectoderm of the primitive oral cavity called []
The anterior pituitary is derived from an upgrowth from the oral ectoderm of the primitive oral cavity called Rathke’s pouch
What are the three types of cells in the AP? [3]
What are their differing roles?
Acidophil:
* Pink cytoplasm and dark nuclei
* Secrete protein hormones: growth factor and prolactin
Basophils
* Purple cytoplasm
* Secrete glycoprotein hormones: adrenocorticotrophic hormone,
thyroid stimulating hormone, follicle
stimulating hormone and luteinizing hormone
Chromophobe
* Non secretory serve as support or
precursors for acidophils and
basophils
What are the types of capillaries in the AP? [1]
The capillaries in this gland are fenestrated, to enable passage of hormones from the secretory cells into the bloodstream.
Which AP cells are which on the masson trichrome? [2]
Posterior Pit:
The [] portal circulation carries releasing hormones from the [] to the [] targeting the [] and [] and causing release of hormones into the blood stream.
the hypophyseal portal circulation carries releasing hormones from the hypothalamus to the adenohypophysis targeting the acidophils and basophils and causing release of hormones into the blood stream.
The bulk of the PP consists of axons from neurons in the [] and [] nuclei of the hypothalamus
The bulk of the PP consists of axons from neurons in the supraoptic and paraventricular nuclei of the hypothalamus
Label A of PP
Herring Bodies
What are the 3 divisions of the adrenal cortex? [3]
- Glomerulosa (near capsule)
- Fasiculata
- Reticularis (near medulla)
What are the cells of the adrenal medulla called? [1]
What do they produce? [1]
What are the cells of the adrenal medulla called? [1]
Chromaffin cells
What do they produce? [1]
catecholamines (adrenaline and noradrenaline)
How would an adenoma affect adrenal cortex?
- Adenoma = a benign tumour of glandular
origin - e.g. increase in cortisol
What is pheochromocytoma?
Name 3 symptoms
- Grows from the chromaffin cells
- Most are benign only about 10% metastasise
to other parts of the body - Very rare (8 people per 1 million) * Classic triad of episodic (in around 30%)
- Headaches
- Sweating
-
Tachycardia
due to increased adrenaline release - Fine granular cytoplasm can be deeply basophilic
- Granules are filled with catecholamines
- Nuclei round or oval with one or more nucleoli
Label A1 and A2 B C
A1: Follicles
A2: colloid (and a central mass of follicles)
B: Follicular epithelial cells
C: LCT
Why do follicular epithelial cells change in shape and how does this occur? [2]
Follicular cells - are almost columnar in appearance in some regions, whilst elsewhere they have a low cuboidal appearance.
This is because in active glands, the follicles are smaller, and have reduced colloid - the cuboidal lining cells are relatively tall because they are actively making and secreting hormones - so packed full of ER and golgi.
Hypothyroidism = squamous or cuboidal Hyperthyroidism = columnar
Explain characterisitcs of Hashimoto thyroidosis
- Autoimmune disease of T
- Causes hypothyrodism due to destruction of TSH receptor
- Lympocyte infiltration occurs
Identify the clusters of chief cells (CC), which secrete PTH. Also, identify oxyphil cells (OC), which are larger and paler staining than the chief cells.
What is the role of D-cells in islet of langehans? [1]
What is the role of D-cells in islet of langehans?
Produce somatostatin broad effects on gastrointestinal function, inhibits insulin and glucagon secretion
Which of the following is the thyrocervical trunk? [1]
48
Label A-C of the liver
Which liver pathology is occurring here? [1]
cholestasis
Liver injury with cholestasis typically results in an increase of what laboratory value?
Alanine aminotransferase
Albumin
Alkaline phosphatase
Aspartate aminotransferase
Liver injury with cholestasis typically results in an increase of what laboratory value?
Alanine aminotransferase
Albumin
Alkaline phosphatase
Aspartate aminotransferase
What is this adrenal histopathology depicted? [1]
Pheochromocytoma
What is this adrenal histopathology depicted
Adrenalectomy with pheochromocytoma. Thin fibrous bands impart a nested look to pheochromocytoma.
Name this liver disease [1]
steatosis
A 60 year old man was admitted with massive hematemesis and hypovolemic shock. He failed to respond to resuscitation. Postmortem examination revealed a liver shown as above. What is the most likely cause of his massive gastrointestinal bleeding?
Acute gastritis
Aortoesophageal fistula
Esophageal varices
Hepatocellular carcinoma
Peptic ulcer
A 60 year old man was admitted with massive hematemesis and hypovolemic shock. He failed to respond to resuscitation. Postmortem examination revealed a liver shown as above. What is the most likely cause of his massive gastrointestinal bleeding?
Acute gastritis
Aortoesophageal fistula
Esophageal varices
Hepatocellular carcinoma
Peptic ulcer
What is this liver pathology? [1]
cirrhosis
What is this liver pathology? [1]
What is this liver pathology?
Chronic cholecystitis characterized by gallbladder wall thickening secondary to muscularis hypertrophy, with a dilated Rokitansky-Aschoff sinus and adjacent transmural lymphoid aggregate.
What is this liver histology? [1]
