Metabolism 2 Wk1+2 Flashcards

Question

explain (simply) how most of alcohol is broken down

Answer 1

ADH PATHWAY; Most of the ethanol in the body is broken down in the liver by an enzyme called alcohol dehydrogenase (ADH), which transforms ethanol into a toxic compound called acetaldehyde (CH3CHO), a known carcinogen. However, acetaldehyde is generally short-lived; it is quickly broken down to a less toxic compound called acetate (CH3COO-) by another enzyme called aldehyde dehydrogenase (ALDH). Acetate then is broken down to carbon dioxide and water, mainly in tissues other than the liver.

Answer 2

The mutation in aldehyde dehydrogenase 2, or ALDH2. Variants in this gene are associated with facial redness following alcohol consumption. These mutations cause the activity of the enzyme to be greatly reduced, resulting in the buildup of acetaldehyde, a toxic product of alcohol metabolism

Answer 3

hypothalamic-pituitary-adrenal (HPA) axis is your body's main way of responding to stress 1) Stress happens HPA Axis Components: Hypothalamus: Releases Corticotropin-Releasing Hormone (CRH). Pituitary Gland: Releases Adrenocorticotropic Hormone (ACTH). Adrenal Glands: Release cortisol, the main stress hormone. Cortisol’s Role: Increases blood sugar for energy. Mobilizes metabolic resources. Temporarily suppresses non-essential functions (e.g., immune system, digestion). Acts as an anti-inflammatory. Negative Feedback Loop: High cortisol levels signal the hypothalamus and pituitary to reduce CRH and ACTH release, helping to balance the system. Chronic Stress Impact: Long-term HPA activation can lead to immune dysfunction, metabolic disorders, and mental health problems. Dysregulation can cause HPA axis fatigue or adrenal insufficiency.

Answer 4

1. Alcohol Dehydrogenase (ADH) Pathway: 80-90% of ethanol breakdown. It primarily occurs in the liver, but also in the stomach (particularly in males). Step 1: Conversion of Ethanol to Acetaldehyde Enzyme: Alcohol Dehydrogenase (ADH) Reaction: Ethanol is oxidized to acetaldehyde. Coenzyme: NAD⁺ (Nicotinamide Adenine Dinucleotide) is reduced to NADH in this process. Step 2: Conversion of Acetaldehyde to Acetate Enzyme: Aldehyde Dehydrogenase (ALDH) Reaction: Acetaldehyde, a toxic compound, is quickly converted to acetate. Coenzyme: NAD⁺ is again reduced to NADH. Acetate is further broken down into carbon dioxide (CO₂) and water (H₂O) in peripheral tissues, particularly muscles, where it enters the citric acid cycle (TCA cycle). Key Points: NADH accumulation: Excess NADH can disrupt cellular metabolism, causing issues like fatty liver. Acetaldehyde: It is a highly reactive and toxic compound, contributing to hangover symptoms. 2. Microsomal Ethanol-Oxidizing System (MEOS) The MEOS pathway comes into play during heavy or chronic alcohol consumption when the ADH pathway becomes saturated (10-20% ethanol breakdown). It is part of the liver's cytochrome P450 enzyme system, specifically CYP2E1. Biochemistry of MEOS Pathway Enzyme: CYP2E1, part of the cytochrome P450 family. Reaction: Ethanol is oxidized to acetaldehyde using NADPH and oxygen (O₂). Key Points: Increased Enzyme Activity: Chronic alcohol use induces more CYP2E1 production, enhancing the MEOS pathway. Reactive Oxygen Species (ROS): This pathway generates ROS, which can cause liver damage (oxidative stress). Drug Interactions: CYP2E1 also metabolizes certain drugs, leading to potential drug interactions and toxicities. 3. Catalase Pathway The catalase pathway is a minor route, contributing less than 2% to total alcohol metabolism. It occurs primarily in the peroxisomes of liver and BRAIN. Biochemistry of Catalase Pathway Enzyme: Catalase Reaction: Ethanol is oxidized to acetaldehyde using hydrogen peroxide (H₂O₂) as an oxidizing agent. Key Points: Limited Contribution: Plays a small role in overall alcohol metabolism. Functional in the Brain: May be relevant in the brain where catalase activity is higher, potentially linking alcohol to its central nervous system effects.

Answer 5

Acetaldehyde, a metabolite of ethanol (ie alcohol) is eventually excreted from the body as acetic acid. But before its conversion to acetic acid, acetaldehyde contributes to the symptoms of a hangover

Answer 6

GABA is an inhibitory neurotransmitter; ethanol activates GABA. So ethanol potentiates GABA-A via allosteric modulation. Increases frequency of chloride channel opening= high chloride influx= Inhibitory post synaptic potentials (iPSPs) this activation of GABA receptors= suppression of glutamate non-competitive antagnonist of NMDA receptors upregulation of NMDA receptors= rebound effect

Answer 7

ataxia, dysmetria= cerebellum is affected by GABA increase esp. decreased function of purkinje cells. Basal ganglia effected by GABA/glutamate increase due to alcohol Nystagmus= rapid-uncontrollable eye movements causing blurred vision; alcohol disturbs cerebellum inducing gaze-evoked nystagmus delayed reaction time= motor cortices have depressed cortical activity, as alcohol inhibits spinal reflexes and suppresses of proprioception nausea/vomiting= potentiates 5HT3 memory problems= GABA (increases when drunk) dampens memory pain relief= alcohol activates endogenous opioid systems; endorphins + enkephalins happy feelings/ mood altered= increase dopamine, acts on serotonin receotirs 5HT3, 5HT2 causing mood altering effects addiction/ feelings of joy= increases dopamine in nucleus accumbens-- influence dopamine transporters

Answer 8

* neurodegeneration + brain atrophy; particularly in frontal lobes, cerebellum, hippocampus= all cause cognitive impairment * loss of white matter integrity= corpus callosum atrophy * psych disorders= Wernicke-Korsakoff syndrome (vision changes, ataxia, memory probs), depression, anxiety, alcohol induced psychosis (delirium tremens) n.b. delirium tremens is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, shivering, irregular heart rate, and sweating. People may also hallucinate * hepatic encephalopathy= alcoholic cirrhosis * addiction + tolerance/cross tolerance * alcoholic polyneuropathy= thiamine deficiency

Answer 9

atrophy= decrease in size

Answer 10

Beriberi is a disease caused by vitamin B1 deficiency, also known as thiamine deficiency. It occurs most often in people with a diet that consists mostly of white rice or highly refined carbohydrates Symptoms: Difficulty walking. Loss of feeling (sensation) in hands and feet. Loss of muscle function or paralysis of the lower legs. Mental confusion. Pain. Speech difficulties. Strange eye movements (nystagmus) Tingling. Good sources of thiamine: peas. some fresh fruits (such as bananas and oranges) nuts. wholegrain breads. some fortified breakfast cereals. liver (avoid liver if you are pregnant)

Answer 11

- low nasal bridge -top of ear underdeveloped -epicanthal folds -indistinct philtrum -thin upper lip -curved fifth finger (clinodactyly) -underdeveloped jaw -short nose -small eye openings * hyperactive behaviour * learning difficulties * various developmental delays

Answer 12

Melaena refers to black, tar-like, sticky stools and usually results from upper gastrointestinal bleeding

Answer 13

Site Onset Character, Radiation, Associated features, Time course, Exacerbating or alleviating factors, Severity

Answer 14

- pain in jaw -abdominal pain -tearing pain in the back -syncope

Answer 15

Lichen planus is a rash that can affect different parts of your body, including inside your mouth. Symptoms of lichen planus include raised purple-red blotches on your skin, white patches in your mouth and bald patches on your scalp. Causes can be Hepatitis C, a virus that attacks your liver. Certain medicines, including some drugs used to treat high blood pressure, diabetes, heart disease, and malaria. Reactions to metal fillings in your teeth.

Answer 16

Diverticulitis= is inflammation of irregular bulging pouches in the wall of the large intestine Symptoms of diverticulitis: pain in the lower left side of your tummy (abdomen) – a small number of people get pain on the right side. tummy pain that gets worse after you eat, and gets better after you poo or fart. constipation. diarrhoea. blood in your poo. bloating.

Answer 17

Claudication is pain in the legs or arms that occurs while walking or using the arms

Answer 18

tachycardia abdominal distention guarding (involuntary reaction to protect an area of pain) cullen's sign (Cullen's sign is described as superficial oedema with bruising in the subcutaneous fatty tissue around the peri-umbilical region. This is also known as peri-umbilical ecchymosis. It is most often recognised as a result of haemorrhagic pancreatitis or ruptured ectopic pregnancy)

Answer 19

THE DIFFERENCE IS CULLENS IS PERIUMBILICAL BRUISING WHEREAS GREY TURNER'S IS BRUISING OF FLANKS cullen's sign= indicated haemorrhagic pancreatitis or ectopic pregnancy grey turner's sign= severe acute necrotizing pancreatitis

Answer 20

Acute onset of abdominal pain which might be generalised or in the upper part of the abdomen Pain that might radiate to the back or flank nausea fever

Answer 21

Located one-third of the distance from the anterior superior iliac spine to the navel on the right: Appendicitis McBurney's point is the clinical point of the bottom of the appendix= if patient has appendicitis theyd have severe pain here

Answer 22

Rovsing's sign= Palpation of the left lower quadrant increases the pain felt in the right lower quadrant

Answer 23

Severe unilateral pelvic pain vaginal bleeding Referred pain to the shoulder fainting

Answer 24

pretibial myxoedema= a skin condition that causes plaques of thick, scaly skin and swelling of your lower legs. This condition is a form of Graves' disease and can affect people diagnosed with thyroid conditions. Symptoms are cosmetic and the condition doesn't always need treatment (common in Grave's dermopathy)

Answer 25

Vaginal discharge Fever Dyspareunia (painful sexual intercourse) Pelvic pain

Answer 26

Patient abruptly holds his/her breath if taking a deep breath in on palpation in the right subcostal area of the abdomen A positive Murphy's sign is seen in acute cholecystitis; because u have touched their inflammed gallbladder

Answer 27

Chron's disease= inflammation of gut which can lead to belly pain, severe diarrhoea, fatigue, weight loss and malnutrition. symptoms: diarrhoea, stomach aches and cramps, and blood in your poo. The main treatments for Crohn's disease are medicines that reduce inflammation in your gut and stop it coming back. Some people need to have surgery.

Answer 28

aka fluid wave test/ fluid thrill test is performed to assess for ascites (free fluid in peritoneal cavity) fluid thrill= felt as a ripple of fluid against one's hand. It can be seen in patients with very obvious ascites It is performed by having the patient push their hands down on the midline of the abdomen. The examiner then taps one flank, while feeling on the other flank for the tap.

Answer 29

Transmission: Fecal-oral route. Incubation: 2–6 weeks. Does NOT cause a carrier state or chronic infection.

Answer 30

Transmission: Parenteral, sexual, perinatal. Incubation: 4–20 weeks. Carrier state and chronic hepatitis possible (5–10% in adults, higher in neonates).

Answer 31

Transmission: Parenteral (IV drug use, transfusions). Incubation: 2–26 weeks. Chronicity (=long-lasting disease) is very common (~80%).

Answer 32

1) Dependent on HBV infection. Can occur as a coinfection or superinfection, with superinfection having higher chronicity and worse outcomes. 2) Coinfection: HDV and HBV are contracted simultaneously. Often acute and self-limited. Superinfection: HDV is acquired after HBV infection. Higher risk of severe hepatitis and progression to cirrhosis.

Answer 33

Carrier state: A person harbours the virus (e.g., HBV or HCV) but may or may not have symptoms. They can still transmit the virus, especially HBV, and are at risk of chronic liver disease.

Answer 34

- Immune-mediated damage, rather than the virus itself, causes acute liver injury: ○ Cytotoxic T cells target infected hepatocytes. ○ Overactive immune responses can lead to fulminant hepatitis (acute liver failure; when your liver begins to fail very quickly within days or weeks.) In chronic hepatitis, ongoing immune activation causes fibrosis and cirrhosis.

Answer 35

Acute hepatitis: Hepatocyte necrosis, apoptosis, and inflammation. Subfulminant hepatitis: Less rapid but significant hepatic dysfunction. Fulminant hepatitis: Massive hepatocyte loss, liver failure within weeks.

Answer 36

Direct Hepatotoxicity (Intrinsic): Predictable, dose-dependent liver injury. Examples: Paracetamol overdose, alcohol, industrial chemicals. Leads to acute liver failure or necrosis. Idiosyncratic Drug-Induced Liver Injury (DILI): Unpredictable, dose-independent, mediated by immune or metabolic reactions. Examples: Antibiotics (e.g., co-amoxiclav), anti-epileptics (e.g., phenytoin), herbal supplements. Cholestatic Liver Injury: Impaired bile flow due to drugs or toxins. Examples: Anabolic steroids, contraceptive pills, erythromycin. Steatohepatitis (Fatty Liver): Toxin-induced fat accumulation in the liver, sometimes progressing to inflammation. Examples: Alcohol, corticosteroids, tamoxifen (breast cancer med). Chronic Hepatitis or Fibrosis; Long-term injury from repeated exposure. Examples: Aflatoxins, alcohol, or chemotherapy agents (e.g., methotrexate). Autoimmune-like Hepatitis; Drug-induced immune-mediated inflammation resembling autoimmune hepatitis. Examples: Nitrofurantoin, hydralazine, minocycline. Vascular or Ischaemic Liver Injury; Linked to drugs causing altered hepatic blood flow. Examples: Chemotherapy drugs (e.g., oxaliplatin) and anabolic steroids. Clinical Implications Recognition: Timely identification is critical to prevent progression to cirrhosis or acute liver failure. Treatment: Stop the causative drug immediately. Use specific antidotes if available (e.g., N-acetylcysteine for paracetamol overdose). Monitoring: Patients on high-risk drugs should have regular liver function tests.

Answer 37

HAV: Anti-HAV IgM: Indicates acute or recent HAV infection. Significance: Positive in the early stages of infection, often resolving within months. Anti-HAV IgG: Indicates: Immunity following recovery or vaccination. Significance: Shows past infection or immunization; lifelong protection. HBV: HBsAg: Active infection. Anti-HBs: Immunity (from vaccine or resolved infection). Anti-HBc: Past or chronic infection. HBeAg: High infectivity. HBV DNA: Viral load. HCV: Anti-HCV: Past or current infection (needs confirmation with HCV RNA). HDV: Anti-HDV IgM: Acute infection. Anti-HDV IgG: Chronic or past infection. N.B. A GOOD RULE HERE IS IgM= acute infection IgG= chronic infection

Answer 38

* virus targets liver cells (hepatocytes) and make the hepatocytes present abnormal proteins via MHC Class I molecules (on hepatocytes) * immune cells infilitrate liver; CD8+ T cells kill the hepatocyte (since its presenting)= this cytotoxic killing causes hepatocyte apoptosis * a hepatocyte undergoing apoptosis u see on histological pic as COUNCILMAN BODY (typically seen in portal tracts or lobules of liver)

Answer 39

Hepatitis D can only infect a host that has Hepatitis B. coinfection= infected with HDV and HBV at the same time superinfection (more severe)= infected with HBV first then later with HDV

Answer 40

Differences in Types of Hepatitis Viral Hepatitis (e.g., HBV, HCV): Dominated early by NK cells, CD8+ T cells, and Kupffer cell activation. Autoimmune Hepatitis: Early infiltration by CD4+ T cells and macrophages. Alcoholic/Non-Alcoholic Steatohepatitis (ASH/NASH): Neutrophils and monocyte-derived macrophages are prominent early responders. Drug-Induced Hepatitis: Neutrophils and monocytes are often the first infiltrators, responding to hepatocyte damage.

Answer 41

If bilirubin is elevated in isolation (i.e., without significant increases in liver enzymes like ALT, AST, or alkaline phosphatase), it suggests that the underlying issue is likely related to unconjugated hyperbilirubinemia causes: -Gilbert's syndrome (not dangerous): asymptomatic; genetic condition causes reduced activity of the enzyme UDP-glucuronosyltransferase (UGT1A1), which conjugates bilirubin. -Crigler-Najjar Syndrome (Rare but can cause fatal brain damage): severe deficiency or absence of UGT1A1. -Haemolysis (Subclinical or Mild): Increased breakdown of RBCs leads to excess heme and unconjugated bilirubin production. -Rotor Syndrome or Dubin-Johnson syndrome(not dangerous): defect in bilirubin storage and transport, causing conjugated hyperbilirubinemia= causes benign, non-haemolytic jaundice

Answer 42

Acetaminophen (Paracetamol) Overdose: Clinical Signs/Symptoms: Nausea, vomiting, abdominal pain (especially RUQ). Jaundice, confusion (indicating encephalopathy in severe cases). Progression to acute liver failure if untreated. Blood Work: Elevated AST/ALT: Extremely high (often >1000 IU/L). INR/PT: Prolonged due to impaired liver function. Bilirubin: Elevated in later stages. Acetaminophen level: Assessed using the Rumack-Matthew nomogram to determine toxicity risk. Lactate: Elevated in severe liver failure.

Answer 43

Isoniazid-Induced Hepatitis: Clinical Signs/Symptoms: Fatigue, nausea, abdominal pain, and jaundice. May progress to fulminant hepatitis. Blood Work: Elevated AST/ALT: Moderate to severe elevation. Bilirubin: Increased in more severe cases. Liver function tests (LFTs): Decompensation seen in advanced damage. Autoantibodies: Occasionally detected (suggesting immune-mediated damage).

Answer 44

YES ; In alcohol-induced hepatitis, AST is typically greater than ALT, with an AST/ALT ratio greater than 2:1 being characteristic. This pattern occurs because: Alcohol's effects on mitochondria: Alcohol damages hepatic mitochondria, where ALT is located, reducing its release into the bloodstream. AST, which is found in both the cytoplasm and mitochondria, is released in higher amounts. Vitamin B6 deficiency: Chronic alcohol use can lead to vitamin B6 deficiency, impairing ALT synthesis more than AST.

Answer 45

in viral hep ALT is greater than AST (ALT is also the last to return to normal)

Answer 46

Alcohol: Clinical Signs/Symptoms: Hepatomegaly, RUQ pain, nausea, vomiting. Jaundice, spider angiomata, palmar erythema (in chronic alcohol use). Blood Work: AST/ALT ratio >2:1: AST typically elevated but rarely >500 IU/L. GGT: Elevated due to alcohol metabolism. Bilirubin: Elevated in severe cases. INR/PT: Prolonged in significant liver dysfunction. Macrocytosis (MCV >100 fL): Commonly seen in chronic alcohol use.

Answer 47

Amanita phalloides (Mushrooms): Clinical Signs/Symptoms: Delayed onset of symptoms (6-12 hours post-ingestion): Nausea, vomiting, diarrhea. Later signs include jaundice, confusion, bleeding, renal failure. Blood Work: AST/ALT: Extremely elevated (often >2000 IU/L). Bilirubin: Elevated as liver failure progresses. Coagulation studies: INR/PT prolonged. Amatoxin levels: If available, can confirm diagnosis. Lactate: Elevated in severe metabolic acidosis.

Answer 48

Autoimmune Hepatitis: Clinical Signs/Symptoms: Fatigue, jaundice, pruritus, arthralgia. In severe cases: ascites or encephalopathy. Blood Work: AST/ALT: Moderately elevated (can reach several hundred IU/L). Bilirubin: Elevated in advanced cases. Autoantibodies: ANA (antinuclear antibody). SMA (smooth muscle antibody). Anti-LKM-1 (liver kidney microsome). IgG levels: Markedly elevated. Liver biopsy: Confirms interface hepatitis.

Answer 49

Budd-Chiari Syndroms: Clinical Signs/Symptoms: Sudden onset of RUQ pain, hepatomegaly, ascites. Jaundice, leg swelling (from portal hypertension). Blood Work: AST/ALT: Elevated but not extremely high. Bilirubin: Elevated. Albumin: Low in chronic cases. Coagulation studies: INR/PT may be prolonged. Imaging Studies: Doppler ultrasound or CT/MRI: Shows hepatic vein thrombosis.

Answer 50

Wilson’s Disease: Clinical Signs/Symptoms: Kayser-Fleischer rings (visible with slit lamp). Fatigue, jaundice, psychiatric symptoms (e.g., depression, personality changes). Neurological signs: Tremor, dystonia. Blood Work: AST/ALT: Modest elevation. Ceruloplasmin: Low (<20 mg/dL). Serum copper: Low. Urinary copper: Elevated (24-hour collection). Liver biopsy: Confirms copper deposition. Coombs-negative hemolytic anemia: Seen in acute Wilsonian crises.

Answer 51

exocrine= (have ducts) secretions produced by the gland e.g. sweat glands, salivary glands, mammary glands, sebaceous glands, lacrimal glands, PANCREAS endocrine= (ductless glands) no connecting tube to exterior hormones are secreted into the blood e.g. pituitary, hypothalamus, thyroid, pancreas and adrenals all secrete products directly into blood N.B. pancreas is 99% exocrine and 1% endocrine

Answer 52

symptoms: -headaches -visual field disturbances -erosion through pituitary fossa cause CSF rhinorrhea signs: - in kids causes gigantism (child has high levels of growth hormone) - increased GH (growth hormone) secretion -acromegaly syndrome (increased chondrocyte mitosis in epiphyseal growth plates= increased osteoblast activity)

Answer 53

the thyroid gland is located in the anterior triangle of the neck and it [produces hormone involved in metabolism regulation and calcium homeostasis. The thyroid is surrounded by a fibrous capsule inside the PRETRACHEAL fascia

Answer 54

thyroid: arterial supply: -superior thyroid artery from external carotid artery -Inferior thyroid artery from a branch of subclavian artery venous drainage: -superior + middle thyroid veins drain into internal jugular vein -Inferior thyroid arteries drain into brachiocephalic veins

Answer 55

larynx arterial supply: -superior laryngeal a. from superior thyroid a. via external carotid a. -inferior laryngeal a. from inferior thyroid a. from the thyrocervical trunk via the subclavian a. venous drainage: -superior laryngeal vein; drains upper larynx + empties into superior thyroid vein, which then drains into internal jugular vein - inferior laryngeal vein; drains lower larynx + empties into inferior thyroid vein, which then drains into the left brachiocephalic vein

Answer 56

superior laryngeal nerve (external branch/EBSLN)= supplies ONLY cricothyroid muscle superior laryngeal nerve (internal branch/ IBSLN)= pierces thyroid membrane to supply mucosa of the larynx above true vocal cords -recurrent laryngeal nerve= motor to all laryngeal muscles EXCEPT cricothyroid muscle

Answer 57

Graves Disease (aka toxic diffuse goitre disease) is an autoimmune disease which causes hyperthyroidism (most common cause of hyperthyroidism). signs: -Results in enlarged thyroid -thickening of skin on shins (pretibial myxodema) - eye bulging/ exophthalmos (Graves' ophthalmopathy) symptoms: (think mania) - irritability -muscle weakness -sleep problems -fast heartbeat -diarrhoea -unintentional weight loss -poor heat tolerance

Answer 58

pancreas arterial supply: -ultimately via several branches of coeliac trunk -branches from splenic a. and from gastroduodenal a. venous drainage: -tributaries drain to the splenic vein + to superior mesenteric vein

Answer 59

synthesis: * Insulin is synthesised in beta cells of pancreas. * transcription from insulin gene *mRNA stability + translation * post-translational modifications secretion: - glucose enters beta cells - glucokinase acts as glucose sensor - increase ATP/ADP ratio closes ATP-sensitive K+ channels= depolarisation of plasma membrane - This opens v-g Ca2+ channel. Increase intracellular Ca2+ triggers secretion of insulin-containing granules

Answer 60

* in muscles + adipocytes insulin stimulates glucose uptake= insulin-induced Akt activation stimulates GLUT4 translocation to (and insertion into) the plasma membrane + glucose uptake * in muscles insulin stimulates glycogenesis (glycogen synthesis)= Akt phosphorylates + inactivates glycogen synthase kinase (GSK) this allows activation of gylcogen synthase (GS) * in adipocytes -insulin stimulates lipogenesis (increased glucose uptake; activation of AcetylCoA carboxylase; increased expression of lipogenic genes) -insulin inhibits lipolysis (insulin inhibits lipase; inhibiting hydrolysis of trigylcerides; Malonyl-CoA inhibits transport of acyl-CoA into mitochondria via CPT-1= inhibition of free fatty acids beta oxidation) * in the liver insulin - enhances glucose uptake, increases glycogen synthesis, increases lipogenesis - inhibits gluconeogenesis

Answer 61

- reduced glucose uptake - increase gluconeogenesis

Answer 62

The glucagon receptor is a G protein-coupled receptor (GPCR) n.b. upon ligand binding GTP displaces GDP on the alpha subunit

Answer 63

in the liver glucagon inhibits glycolysis + increases gluconeogenesis cAMP/PKA=

Answer 64

beta oxidation of fatty acids

Answer 65

How Cortisol Works (Mechanism of Action): Hormone Binding: Cortisol enters cells because it’s a fat-soluble hormone. Inside the cell, it binds to glucocorticoid receptors (GRs) in the cytoplasm. Activation & Nucleus Entry: The cortisol-receptor complex becomes active and moves into the cell’s nucleus. Gene Regulation: Inside the nucleus, it binds to specific parts of DNA (glucocorticoid response elements). This changes the activity of certain genes, either increasing or decreasing the production of proteins. Key Effects of Cortisol: Metabolic Effects: Raises blood sugar by increasing glucose production in the liver (gluconeogenesis). Breaks down proteins in muscles for energy. Breaks down fat but can lead to fat buildup in specific areas like the belly or face. Anti-Inflammatory Effects: Blocks the production of inflammation-causing chemicals (e.g., prostaglandins, cytokines). Reduces immune cell activity (e.g., T-cells), suppressing the immune system. Stress Response: Helps the body cope with stress by maintaining blood sugar and blood pressure. Cardiovascular Effects: Makes blood vessels more responsive to adrenaline, helping maintain blood pressure. Electrolyte Balance: In high amounts, cortisol can act like aldosterone, leading to sodium retention and potassium loss. Control and Regulation: Cortisol is regulated by the HPA axis: Hypothalamus → Releases CRH. Pituitary gland → Releases ACTH. Adrenal glands → Release cortisol. Cortisol provides negative feedback, shutting down CRH and ACTH when levels are high. Clinical Relevance: Too much cortisol (Cushing's Syndrome): Causes weight gain, high blood sugar, high blood pressure, weak muscles, and suppressed immunity. Too little cortisol (Adrenal Insufficiency): Causes fatigue, low blood pressure, weight loss, and low blood sugar. Therapeutic Uses: Synthetic cortisol is used to treat inflammation (e.g., arthritis), autoimmune diseases, and adrenal insufficiency.

Answer 66

1. Synthesis of Glucagon Precursor: Synthesized as preproglucagon in pancreatic α cells. Processing: Converted to proglucagon → further processed by enzymes into active glucagon. Storage: Stored in secretory granules until release. 2. Secretion of Glucagon ✅ Stimulated by: Low blood glucose (hypoglycemia) – Increases glucose production. High amino acids (protein intake) – Prevents hypoglycemia. Sympathetic activation (stress/exercise) – Mobilizes energy. ❌ Inhibited by: High blood glucose (hyperglycemia) Insulin – Signals sufficient glucose. Somatostatin – Inhibits secretion. 3. Mechanism of Secretion Glucose sensing: Low glucose → α cells release glucagon. Calcium signaling: Triggers glucagon granule exocytosis. 4. Effects of Glucagon Glycogenolysis – Breaks down glycogen → glucose. Gluconeogenesis – Converts non-carbs (amino acids, lactate) → glucose. Lipolysis (indirect) – Mobilizes fat for energy. 💡 Summary: Made in α cells, stored, and released when glucose is low. Opposes insulin, ensuring stable blood sugar.

Answer 67

in the post absorptive state, all tissues except LIVER use glucose as fuel. Muscle + adipose tissue reduce their glucose utilisation

Answer 68

ketone bodies are the main fuel source during prolonged fasting (they're also synthesised during fasting/prolonged exercise)

Answer 69

starvation= loss of intracellular stores of many electrolytes (phosphate + potassium) refeeding= YOU HAVE TO GIVE ELECTROLYTES can't just give food! Insulin goes up and then electrolytes leave cell= very dangerous as serum levels of electrolytes already low this can cause= hypophosphataemia, hypokalamia, thiamine deficiencies which lead to congestive heart failure + peripheral oedema

Answer 70

glycogenolysis

Answer 71

GLYCOLYSIS is inhibited in the liver. Liver synthesises new glucose (GLUCONEOGENESIS) from amino acids, lactate, glycerol

Answer 72

triglycerides are broken down in adipose tissues (LIPOLYSIS) to provide glycerol (used in gluconeogenesis) + fatty acids

Answer 73

The brain and red blood cells (RBCs) are the primary tissues that cannot use fatty acids for ATP production.

Answer 74

Oxaloacetate is used by the liver as a substrate for gluconeogenesis

Answer 75

KETOGENESIS= Excess acetyl-CoA is converted into ketone bodies by the liver

Answer 76

Ketogenesis is inhibited by INSULIN and activated by GLUCAGON

Answer 77

- decrease in number of insulin receptor -decrease in catalytic activity of receptor -increased activity of tyrosine phosphatases -decreased levels and function of GLUT4 -increased Serine/Threonine phosphorylation of the receptor or of IRS (insulin receptor substrate) -decrease PI3K/Akt activity

Answer 78

- new beta cells can be generated in response to insulin resistance associated w obesity + pregnancy (replication of mature beta cells + neogenesis of precursors) -islets increase in both size + number due to beta cell increase -there is also INCREASED beta function -glucose tolerance cna be maintained by increased insulin secretion

Answer 79

H+ and Ca2+ both bind to albumin ACIDOSIS= increased H+, decreased blood pH= decreases calcium binding to albumin= increased in ionised calcium (CA2+)= hyPERcalcaemia ALKALOSIS= decreased H+, increased blood pH= increases calcium binding to albumin= decrease in ionised calcium (CA2+)= hypOcalcaemia (deadly; causes tetany, paresthesia, seizures, laryngospasm)

Answer 80

PTH elevates calcium levels by: 1) BONES; Releasing calcium from bone via increased osteoclast-mediated resorption. Increases calcium and phosphate resorption 2) KIDNEYS; Reducing renal calcium excretion by enhancing reabsorption in the kidneys. (n.b. kidneys are the only ones that DECREASE calcium excretion) 3) GUT; Increasing intestinal calcium absorption indirectly through activation of vitamin D. Increases absorption of calcium and phosphate

Answer 81

Technetium-sestamibi scintigraphy is a nuclear medicine imaging technique used to locate and evaluate hyperactive parathyroid tissue, particularly in the diagnosis and management of primary hyperparathyroidism.

Answer 82

if ionised calcium levels rise, PTH levels FALL

Answer 83

CaSR (calcium sensing receptor) - calcium binds to CaSR - reduces PTH secretion -increases breakdown of stored PTH - suppresses transcription of PTH gene -inactivating mutations lead to FHH (Familial hypocalciuric hypercalcemia) -activating mutations lead to hypocalcemic disorders

Answer 84

- activated vitamin D (Calcitriol)= suppreses PTH gene transcription -phosphate= stimulate PTH gene transcription -cinacalcet (a calcimimetic drug treats hyperparathyroidism by allosterically activating CaSR= reduces PTH but drug causes loads of nausea)= activates CaSR and reduces PTH= reduces Calcium levels -CaSR (calcium sensing receptor) activation= restrains parathyroid proliferation

Answer 85

Resorption Definition: The process of breaking down and reclaiming material from an existing structure, typically within the body. e.g. In response to low calcium levels, parathyroid hormone (PTH) stimulates bone resorption, releasing calcium into the blood. Absorption Definition: The process of taking up substances from the external environment or a lumen into the body, often through epithelial cells.

Answer 86

loop diuretics= decrease calcium levels thiazide diuretics= increase calcium levels

Answer 87

patient with hyperparathyroidism are more likely to get T2DM because PTH stimulates GLUCONEOGENESIS if u have hyperactive parathyroid= more PTH= more gluconeogenesis= excess glucose in blood= diabetes

Answer 88

PTH= increases RANKL; decreases OPG; increases IGF1 and IL1=> decreases bone formation if continuous PTH stream, increases bone formation if PTH intermittent Calcitriol= increases RANKL; increases gut calcium absorption=> when sufficient promotes bone formation, when deficient causes bone resorption Glucocorticoid= reduce osteoblast numbers + mineral production= increases RANKL=> causes net bone loss/ increases bone breakdown Estrogen= epiphyseal closure (promotes closure of growth plates during puberty); reduces cytokine sensitivity =>maintains bone density but deficiency leads to bone loss

Answer 89

PTH related peptide (PTHrP) is clinically relevant due to paraneoplastic production causing hypercalcemia of malignancy Elevated PTHrP levels in hypercalcaemic patients with suppressed PTH levels are highly suggestive of malignancy and are associated with a very poor prognosis for long – term survival n.b. PTHrP is important for postpartum lactation

Answer 90

- serum Ca2+ ref range 2.2-2.6 mmol/L clinical presentation: -neuropscyhiatric disturbances -GI abnormalities (constipation/motility probs and pancreatitis) - renal dysfunction (renal stones, nephrogenic diabetes insipidus, renal failure) causes: -malignancy (bone metastasis, Parathyroid related peptide (PTHrP) secretion rarer causes: -FHH -Thiazide diuretic use -Granulomatous disease TREATMENT; just give them a bag of fluid!! expand plasma volume and then treat underlying cause

Answer 91

clinical presentation: - cardiac tachyarrhythmia -tetany -seizures -psychiatric manifestations causes: -PTH problems (hypomagnesemia, autoimmune parathyroidism) -Vitamin D problems (renal/liver failure) -compartmental shifts (hungry bone syndrome, pancreatitis) treatment; u wld need to inject PTH daily but we dont have this treatment so instead give activated vitamin D to increase gut calcium absorption

Answer 92

zona glomerulosa= 11-deoxycorticosternone, aldosterone zona fasciculata= 17OH-progesterone, 11-deoxycortisol, cortisol zona reticularis= dehydroepiandosterone, androstenedione, testosterone

Answer 93

features of hyperaldosteronism; -high BP (hypertension) -low potassium levels (hypokalemia) symptoms as a result; -headaches (cuz uncontrolled hypertension) -Polyuria and Polydipsia (Hypokalemia reduces the kidney's ability to concentrate urine, causing increased urination and thirst.) -fatigue -muscle weakness (low potassium impairs muscle function MAY even lead to paralysis) diagnosis: -metabolic alkalosis (aldosterone causes significant potassium excretion (hypokalemia). Hypokalemia leads to intracellular shift of hydrogen ions to compensate for the reduced extracellular potassium.) -high aldosterone with suppressed renin -aldosterone not falling after infusion of saline (saline suppression test) -CT adrenal - adrenal venous sampling -Metomidate PET treatment: - unilateral adrenalectomy for APA -mineralocorticoid receptor antagonists or potassium sparing diuretics for bilateral disease or patients who can't have an operation

Answer 94

mineralocorticoids are produced in the zona glomerulosa glucocorticoids are produced in the zona fasciculata

Answer 95

ACTH binds to Melanocortin-2 receptor (MC2R)

Answer 96

- Opioids, oxytocin and ANP (atrial natriuretic peptide) inhibit CRH (think heroin addicts can’t produce cortisol/respond to stress) - Stress, catecholamines, Angiotensin II, ghrelin stimulate CRH

Answer 97

Cushing's syndrome= excess cortisol

Answer 98

n.b. Addison's symptoms are initially very vague as body doesn't need to respond to stress all the time, however if u get sick (e.g. flu) u have an addisonian crisis cuz u can't respond to stress Addison's disease= adrenal failure (ur missing aldosterone and cortisol) symptoms: causes: diagnosis: treatment:

Answer 99

Symptoms: - Severe fatigue and weakness - Nausea and vomiting - Abdominal pain - Hypotension (low blood pressure) - Confusion or loss of consciousness Treatment: 1) Immediate administration of intravenous hydrocortisone 2) Fluid resuscitation with saline to address dehydration and electrolyte imbalances

Answer 100

21-hydroxylase insufficiency (as this causes PCOS-like symptoms; amenorrhea, excess hair growth)

Answer 101

-impending doom -palpatations -hyperglycaemia

Answer 102

* phaeochromocytoma (arising from within adrenal medulla) * paraganglioma (extra-adrenal tumours) aka PPGL syndromes (cause tumours) treatment; -surgical resection -pre-operative alpha + beta-blockade -acute crisis; IV phentolamine or nciardipine - AVOID opiates -131lMIBG therapy for malignant disease

Answer 103

phaeochromocytoma= rare tumour of adrenal gland treating w beta blocker is a HUGE MISTAKE!! Because, catecholamine (excess as a result of tumour) stimulate both beta1 and beta2 receptors.. if u block beta2 u have no vasodilation.. Louds of vasoconstriction in someone who already has hypertension.. So u have further raised their blood pressure and they will have a stroke

Answer 104

T1D is a chronic autoimmune disease. It's characterised by disruption of the pancreatic beta cells within the islets of langerhans. aka beta cell autoimmunity. Leading to insulin deficiency Causes: -Autoantibodies present in T1D; islet cell antibodies (ICA, against cytoplasmic proteins in the beta cell), antibodies to glutamic acid decarboxylase (GAD-65), insulin autoantibodies (IAA), and IA-2A, to protein tyrosine phosphatase. -T cells attack beta cells -Genetic predisposition Symptoms: Diagnosis: Treatment:

Answer 105

insulitis= inflammation of the islets of langerhans; particularly, infiltration of the pancreas islets by mononuclear cells.

Answer 106

hyperinsulinaemia= a higher amount of insulin in blood than norm It;s dangerous in T2D as it increases lipid synthesis and exacerbates insulin resistance

Answer 107

- glucotoxicity (hyperglycaemia) -lipotoxicity (increase in circulating FFAs) n.b. combo of both is glucolipotoxicity - hyperinsulinaemia all these together combine to damage the beta cells of the pancreas which limits islet compensation= T2D

Answer 108

-caused by a mutation in a single gene (1of over 40 genes) -this diabetes is due to impairment of insulin secretion/ pancreatic beta cell dysfunction (not synthesis) - accounts for 1-5% of diabetes -most cases are Maturity Onset Diabetes of the Young (MODY)= young age diagnosis, autosomal dominant

Answer 109

Insulin sensitiser drugs increase insulin sensitivity METFORMIN class: biguanides mechanism: reduces liver glucose production (inhibits gluconeogenesis) and increases insulin sensitivity in muscles + fat risk: rare risk of lactic acidosis (esp. in kidney or liver disease patients) side effect: GI issues (nausea, diarrhea) n.b.: 1st line for T2D, doesn't cause hypoglycaemia + can aid weight loss THIAZOLIDINEDIONES (TZDs) class: insulin sensitisers mechanism:activates transcription factor PPARγ receptors in adipocytes. Promoting triglyceride storage in adipose-- improves insulin sensitivity in fat + muscle risk: increase risk of heart failure, weight gain + bone fractures side effect: oedema or weight gain (e.g. with pioglitazone weight gain is main side effect) n.b.: works slowly, usually in combo w other drugs. NOT for patients with heart failure (due to risk of fluid retention and diastolic heart dysfunction)

Answer 110

glucose excretion drugs help kindeys remove glucose from blood by blocking its reabsorption (therefore glucose excreted in urine) EMPAGLIFLOZIN, ERTUGLIFLOZIN, CANAGLIFLOZIN, FARXIGA, INVOKANA class: SGLT2 Inhibitors (Sodium-Glucose Contransporter 2 inhibitors) mechanism: blocks glucose reabsorption in kidneys leading to glucose excretion in urine risk: genital infections, UTIs, DKA (diabetic ketoacidosis) side effect: increase urination, thirst + weight loss n.b.: helps with blood sugar control + can aid in heart failure and kidney disease management

Answer 111

SULFONYLUREAS examples: glibenclamide, gliclazide, glimepiride class: insulin secretagogues mechanism: stimulates pancreas to release more insulin, regardless of blood sugar levels risk: hypoglycaemia (if miss meals or high dose), weight gain cuz increased insulin, CVD risks side effect: hypoglycaemia, weight gain n.b.: often w other meds, NOT suitable for renal impairment. Glimepiride + gliclazide have decreased risk of hypoglycaemia MEGLITINIDES/ PRANDIAL GLUCOSE REGULATORS examples: repaglinide, nateglinide, mitiglinide class: insulin secretagogues mechanism: stimulates pancreas to release more insulin esp. post meals risk: hypoglycaemia esp. if meals skipped side effect: hypoglycaemia, weight gain n.b.: short-acting (repaglinide, nateglinide) taken just before meals

Answer 112

Both increase insulin secretion + decrease glucagon by acting on incretin system (regulates blood sugar post meals) GLP-1 agonists examples: exendin-4, ozempic/semaglutide, exanatide, tirzepatide class: incretin memetic mechanism: mimics effects of GLP-1 to increase insulin release, decrease glucagon, + slows gastric emptying (increases satiety) risk: pancreatitis, thyroid cancer (for liroglutide) side effect: nausea, vomit n.b.: injectable drugs (semaglutide, liraglutide) can help with weight loss + has cardiovascular benefits DPP-4 inhibitors examples: linagliptin, alogliptin class: enzyme inhibitors mechanism: prevents breakdown of GLP-1 (inhibits DPP-4 protease that breaks GLP-1 down) which increases insulin and decreases glucagon risk: rare pancreatitis + joint pain side effect: generally well-tolerated; upper resp infections n.b.: oral meds (sitagliptin, saxagliptin)-- less potent than GLP-1R agonists, but easier to use

Answer 113

Bind to bile acids in intestine which reduces glucose production in liver + improves insulin sensitivity examples: colesevelam, colestipol, cholestyramine class: bile acid binding agents mechanism: lowers LDL; binds to bile acids in intestine, decreases glucose production in liver + improves insulin insensitivity risk: interferes w absorption of other meds side effect: (common) constipation, nausea + abdominal discomfort n.b.: used in combo w other drugs e.g. colesevelam + used to lower LDL cholesterol

Answer 114

Carbohydrate absorption modulators delay carbohydrate break down in intestines-- slowing glucose absorption post meals e.g. MIGLITOL, ACARBOSE, VOLGLIBOSE class: alpha-glucosidase inhibitors mechanism: competitive inhibitors of alpha-glucosidase enzyme which breaks down carbs, delaying glucose absorption risk: GI distress, flatulence, diarrhea side effect: GI distress, flatulence, diarrhea n.b.: taken with meals; less commonly prescribed due to GI side effects

Answer 115

prandial= period of time following a meal post-prandial= post-meal important to know this as many meds esp T2D meds are post-prandial or pre-prandial

Answer 116

Insulin alerts peripheral tissues of blood glucose conc not glucose itself

Answer 117

cortisol stimulates gluconeogenesis and glycogenolysis.

Answer 118

Oesophageal varices are enlarged veins in the esophagus, the tube that connects the throat and stomach. Oesophageal varices (seen in serious liver disease) develop when regular blood flow to the liver is blocked by a clot or scar tissue in the liver

Answer 119

During the 3rd to 4th week of gestation, from the endodermal epithelium of the floor of the pharynx.

Answer 120

It is an outpouching from the pharynx that forms the thyroid primordium and later develops into the thyroid gland.

Answer 121

It is a duct connecting the thyroid primordium to the pharynx during its descent. It degenerates, leaving the foramen cecum at the base of the tongue.

Answer 122

They migrate from the ultimobranchial bodies (developed from the fourth pharyngeal pouch) Parafollicular cells (C cells) scattered throughout the thyroid gland synthesize, store, and secrete calcitonin (thyrocalcitonin). These cells are derived from neural crest cells that fuse with the thyroid gland

Answer 123

TRH (Thyrotropin-Releasing Hormone) is a hormone produced by the hypothalamus. It stimulates the pituitary gland to release TSH (Thyroid-Stimulating Hormone), which in turn regulates the production of thyroid hormones (T3 and T4) by the thyroid gland.

Answer 124

NIS: Grabs iodine from the blood. PDS: Moves iodine into the follicular lumen. TPO: Attaches iodine to thyroglobulin and helps make T3 and T4. TSH: Signals the release of T3 and T4 into the blood. D2: Converts T4 into active T3 in tissues.

Answer 125

1) Iodine Uptake (NIS); - NIS (Sodium-Iodide Symporter): - Follicular cells use this NIS "pump" to grab iodine from the blood. 2) Iodine Transport (PDS) - PDS (Pendrin): - Once inside the cell, iodine is transported into the follicular lumen (space inside thyroid follicle) by this transporter. 3) Thyroglobulin Production - Follicular cells make thyroglobulin (Tg) protein and release it into the follicular lumen. - Thyroglobulin= storage unit for thyroid hormones. 4) Iodination (Thyroid Peroxidase/TPO) - TPO enzyme attaches iodine to thyroglobulin, creating MIT (monoiodotyrosine) and DIT (diiodotyrosine). - Think of this as "tagging" thyroglobulin with iodine. 5) Coupling (TPO) TPO also helps combine: - MIT + DIT = T3 (triiodothyronine) - DIT + DIT = T4 (thyroxine) =These are the active thyroid hormones! 6) Storage - T3 and T4 stay attached to thyroglobulin and are stored in the follicular lumen until needed. 7) Release (TSH Stimulation) TSH (Thyroid-Stimulating Hormone): - When the body needs thyroid hormones, the anterior pituitary gland releases TSH. TSH tells the follicular cells to: - Reabsorb thyroglobulin from the lumen. - Break it down to release T3 and T4 into the bloodstream. 8) Activation (D2) D2 (Deiodinase Type 2): - In tissues, D2 converts T4 (inactive) into T3 (active). - T3 is the more potent form of thyroid hormone

Answer 126

Deiodinases are known to convert thyroid hormone from the prohormone thyroxine (T4) to the bioactive hormone tri-iodothyronine (T3) and convert both T4 and T3 toward their inactive metabolites

Answer 127

Hypothyroidism: upregulated= D2 downregulated= D1, D3 Hyperthyroidism upregulated= D1,D3 downregulated= D2

Answer 128

'hyperthyroidism' and 'thyrotoxicosis' are often used interchangeably; however, hyperthyroidism (pathology) refers specifically to excess production and secretion of T3 and T4 from the pathological overactive thyroid gland. Whereas thyrotoxicosis (symptoms) is the clinical manifestation of symptoms owing to excess T3 and T4 it can be because their thyroid gland is inflamed or they're on too high a dose of levothyroxine or because they have hyperthyroidism

Answer 129

excess T3/T4 increases gluconeogenesis, DECREASES insulin secretion= hence patient loses weight (has higher than normal blood glucose levels) think they're digesting there body because the increase basal metabolic rate

Answer 130

transaminitis= elevated transaminases (liver enzymes)

Answer 131

hyperthyroidism causes pernicious anaemia (B12 deficiency)

Answer 132

High TSH levels usually indicate hypothyroidism, and low TSH levels usually indicate hyperthyroidism.

Answer 133

anti-TSHR antibodies (TRAB) cause hyperthyroidism in Graves patients these are antibodies against the TSH receptor

Answer 134

- Postpartum Thyroiditis – Autoimmune inflammation following pregnancy leading to transient thyrotoxicosis. - Subacute (De Quervain’s) Thyroiditis – Viral infection causing inflammation and release of preformed thyroid hormones - Toxic Multinodular Goiter (Plummer’s disease) – 1 or 2 cells have overactive TSH receptor excessive thyroid hormones + causes cells of thyroid gland to enlarge result is huge goitre - TSH-Secreting Pituitary Adenoma – Rare pituitary tumor causing excessive stimulation of the thyroid gland. - excess iodine - Amiodarone is a class III antiarrhythmic used to treat or prevent heart rhythm disorders, such as atrial fibrillation. SIDE EFFECT IS thyrotoxicosis - struma ovarii (Ovarian teratoma producing thyroid hormones) - hCG-Induced Thyrotoxicosis – High hCG levels (e.g., in hyperemesis gravidarum, molar pregnancy, or choriocarcinoma) stimulating thyroid hormone production - Thyroiditis

Answer 135

Graves' eye disease is caused by retroorbital fibrocytes expressing the TSH-receptor (so the stimulation of them by the anti-TSHR antibodies causes these fibrocytes to become hyperplastic and this scar tissue at back of the eyes pushes the eye forward) - some get better with treatment, some need steroids, some patients will even need radiotherapy

Answer 136

3 different antibodies implicated in Hashimoto's: - anti-TPO (anti-thyroid peroxidase) an enzyme essential for thyroid hormone synthesis, leading to gradual destruction of thyroid tissue and resulting in hypothyroidism - Anti-thyroglobulin (anti-Tg) antibodies – Target thyroglobulin, a precursor to thyroid hormones. - TSH receptor-blocking antibodies (TSHR-blocking Ab) – In some cases, these inhibit thyroid function, though they are more commonly associated with atrophic hypothyroidism.

Answer 137

diagnosis; - decreased TSH (low thyroid stimulating hormone) - increased FT3, FT4 (free thyroxine/T4, free triiodothyronine/T3) management; - Thionamide drugs (Propylthiouracil, Carbimazole) - radioactive iodine I-131 - Thyroidectomy

Answer 138

- Hashimoto's disease - low iodine diet (ppl from mountainous regions where soil low in iodine) - endemic goitre - Lithium (intereferes with sodium-iodide transporter) - cabbage - Infiltrative diseases - Hypopituitarism - Thyroidectomy - Pendred syndrome (genetic mutation of PDS/Pendrin transporter that causes early hearing loss in children; also affects thyroid gland + balance)

Answer 139

diagnosis: - increased TSH - low T4 treatment= Levothyroxine Regular follow-up with TSH and FT4 measurements to adjust medication dosage and ensure euthyroid status Ensuring adequate iodine intake is essential, though excessive iodine should be avoided.

Answer 140

normochromic normocytic anaemia = a type of anemia where red blood cells (RBCs) are of normal size (normocytic) and have a normal hemoglobin concentration (normochromic) but are reduced in number. This suggests that the anemia is due to a decreased production or increased loss of RBCs rather than a deficiency in hemoglobin synthesis or cell size abnormalities other causes of Normochromic Normocytic Anemia: - Chronic Disease: Anemia of Chronic Disease (ACD) (e.g., chronic kidney disease, inflammatory disorders, infections, malignancy) - Bone Marrow Disorders: Aplastic anemia, myelodysplastic syndromes - Hemolysis (RBC destruction): Autoimmune hemolytic anemia, sickle cell disease - Acute Blood Loss: Trauma, gastrointestinal bleeding - Chronic Kidney Disease (CKD): Due to decreased erythropoietin production

Answer 141

RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand): A protein encoded by the TNFSF11 gene, crucial for bone metabolism and immune regulation. Role in Bone Metabolism: - Binds to RANK on osteoclast precursors, promoting their differentiation and activation. - Essential for bone resorption and remodeling; dysregulation can lead to osteoporosis or bone loss. Role in the Immune System: - Involved in lymph node development and dendritic cell survival. Therapeutic Target: - Inhibitors like denosumab are used to treat osteoporosis and bone metastases by blocking RANKL activity.

Answer 142

Temporal branch – frontalis, orbicularis oculi and corrugator supercilii. Zygomatic branch – orbicularis oculi. Buccal branch – orbicularis oris, buccinator and zygomaticus muscles. Marginal Mandibular branch – mentalis muscle. Cervical Branch To Zanzibar By Motor Car

Answer 143

The infrahyroid muscles (sternohyoid, sternothyroid, thyrohyoid, omohyoid) depress the hyoid bone. These muscles are all innervated by ansa cervicalis, except thyrohyoid, which is innervated by C1 via the hypoglossal nerve (CN XII)

Answer 144

The suprahyoid muscles(Stylohyoid, Digastric, Mylohyoid, Geniohyoid), which are found superior to the hyoid bone, are responsible for elevating the hyoid bone, which is important in swallowing.

Answer 145

The liver receives most of its blood supply from the hepatic portal vein, whereas the gall bladder is mainly supplied by the cystic artery. LIVER: arterial supply: Hepatic artery proper (25%) & Hepatic portal vein (75%) venous drainage: Hepatic veins → IVC GALLBLADDER: arterial supply: Cystic artery (from right hepatic) venous drainage: Cystic veins → Portal vein or liver

Answer 146

The upper anal canal, above the dentate line, is lined by simple columnar epithelium. The lower anal canal (below the dentate line), is lined by non-keratinised stratified squamous epithelium.

Answer 147

No, Hepatitis A, unlike Hepatitis B or C, does not typically cause long-term liver damage or cirrhosis; most people recover fully without lasting problems

Answer 148

The inferior thyroid vein, which drains blood from the inferior part of the thyroid gland, drains into the brachiocephalic vein

Answer 149

Right Adrenal Gland: Shape: Pyramidal Arterial Supply: Superior: Branch of inferior phrenic artery Middle: Branch of abdominal aorta Inferior: Branch of renal artery Venous Drainage: Right adrenal vein → IVC (directly) Left Adrenal Gland Shape: Crescent (semilunar) Arterial Supply: Same as right (superior/middle/inferior adrenal arteries). Venous Drainage: Left adrenal vein → left renal vein → IVC (indirect)

Answer 150

the left gastric artery, it supplies the distal oesophagus and the lesser Curvature of the Stomach.

Answer 151

The thyroid gland produces 3 main hormones; T3 (triidothyronine) made by follicular cells T4 (thyroxine) made by follicular cells calcitonin made by parafollicular cells

Answer 152

The anterior pituitary gland produces and releases thyroid-stimulating hormone (TSH)

Answer 153

Congestive hepatopathy primarily affects the centrilobular zone of the hepatic sinusoids Congestive hepatopathy is a unique condition in which blood backs up into the interlobular veins of the liver as a result of chronic congestive heart failure. Congestive hepatopathy results in a distinctive speckled appearance on gross pathology much like a piece of grated nutmeg