Metabolism 2 Flashcards
explain what a hernia is and what type of hernia accounts fro 75% of abdominal hernias
a hernia is a protrusion of peritoneum and viscera such as small intestine through an opening or weakness.
Inguinal hernia’s account for 75% of abdominal hernias
they are usually harmless BUT carry risk of having their blood supply cut off= can become a medical + surgical emergency
what is the sensory and motor function of the genitofemoral nerve
provides sensory innervation to the upper anterior thigh, as well as the skin of the anterior scrotum in males and mons pubis in females. It also provides motor innervation to the cremaster muscle (via its genital branch)
what is a direct hernia
- acquired
*males over 40 highest risk factor
*hernia passes directly through abdominal wall (hesselbach’s triangle)
*rarely enters scrotum
*medial to inferior epigastric vessels
what is a indirect hernia
- usually congenital (patent process vaginalis)
- transverses canal with processus vaginalis
*commonly enters scrotun - lateral to inferior epigastric vessels
what artery supplies each of the following parts of the gut:
* foregut
* midgut
* hindgut
then explain the venous drainage of each too
foregut= supplied by coeliac trunk
foregut= drained by splenic vein
midgut= supplied by superior mesenteric artery
midgut= drained by superior mesenteric vein
hindgut= supplied by inferior mesenteric artery
hindgut= drained by inferior mesenteric vein
n.b. all the veins here drain into the hepatic portal vein which travels up to supply liver
If a gallstone blocks bile leaving the gall bladder when the gall bladder contracts, patient will have upper right quadrant pain (aka bilary colic). Overtime, this recurrence can cause cholechystisis. Explain what cholechystitis is and what the medical exam used to test for it is
Cholechystitis= inflammation of gallbladder due to bile flow obstruction
Murphy’s sign is elicited in patients with acute cholecystitis by asking the patient to take in and hold a deep breath while palpating the right subcostal area. If pain occurs on inspiration, when the inflamed gallbladder comes into contact with the examiner’s hand, Murphy’s sign is positive
what is steatosis and its causes
steatosis= accumulation of circular fat droplets within the hepatocytic cytoplasm
causes of steatosis:
alcoholic liver disease, non-alcoholic fatty liver disease (obesity, type 2 diabetes), drugs, viral hepatitis (hep C)
what is lipofuscin
Lipofuscin is an intralysosomal, polymeric substance, primarily composed of cross-linked protein residues, formed due to iron-catalyzed oxidative processes
The accumulation of lipofuscin within postmitotic cells is a recognized hallmark of aging occurring with a rate inversely related to longevity.
Lipofuscin is a yellow-brown pigment that builds up in cells as a byproduct of normal cellular metabolism. It’s sometimes called “wear-and-tear” or “age pigment” because it accumulates over time, especially in long-lived cells that don’t divide much, like liver cells, neurons, and heart muscle cells.
In the liver, lipofuscin collects within the liver cells (hepatocytes) as the body breaks down fats, proteins, and other molecules. Since it’s made of waste products that cells can’t easily get rid of, lipofuscin can’t be broken down and removed as efficiently as other cellular debris. Over time, it builds up in cells, occupying space and potentially affecting cell function by interfering with cellular metabolism and signaling.
As we age, the amount of lipofuscin in the liver (and other organs) increases because cells have more time to accumulate this waste material, and our bodies become less efficient at removing it.
define cholestasis
cholestasis= condition characterising systemic retention of bilirubin + other solutes eliminated in bile
Bile is a fluid that is made and released by the liver and stored in the gallbladder. Explain how the hepatocytes secrete bile
hepatocytes secrete bile into canaliculi
the canaliculi are defined by tight junctions between adjacent heaptocytes
bile flows through these narrow tubes towards the hepatic (bile) duct
from the bile duct it flow into the biliary tree out of the liver to the gallbladder or intestines
what is an INR blood test
INR= international normalised ratio (marker of how long it takes for your blood to clot–if its high/ prolonged it means it takes your blood too long to clot)
what is meant by the terms ‘grade’ and ‘stage’ when referring to liver biopsy
grade= refers to severity and distribution of inflammation
stage=refers to severity and extent of fibrosis in the liver biopsy
what do high bilirubin levels indicate
Higher than usual levels of bilirubin may indicate different types of liver or bile duct problems. Sometimes, higher bilirubin levels may be caused by an increased rate of destruction of red blood cells (haemolysis)
what are the causes of chronic liver disease?
- alcohol
-fat/metabolic syndrome; non-alcoholic liver disease
-viral hepatitis (HBV/ HCV)
-biliary disease (PBC/PSC)
-autoimmune
-metabolic; haemochromatosis, Wilson’s, A1AT deficiency, amyloid
what is Wilson’s disease
Wilson disease is a genetic disorder that prevents the body from removing extra copper, causing copper to build up in the liver, brain, eyes, and other organs
symptoms:
Tiredness and loss of appetite.
A yellowing of the skin and the whites of the eye, known as jaundice.
Golden-brown or copper-colored rings around the irises of the eyes, known as Kayser-Fleischer rings.
Fluid buildup in the legs or stomach area.
Problems with speech, swallowing or physical coordination.
Primary Biliary Cholangitis (PBC) is a biliary disease. Define PBC, it’s symptoms + treatments
Primary Biliary Cholangitis (PBC) is a chronic and progressive condition that causes inflammation and, eventually, the destruction of the bile ducts that run through your liver. Without working bile ducts, bile backs up in your liver, causing liver damage.
symptoms:
Yellowing of the skin and eyes, called jaundice.
Dry eyes and mouth.
Pain in the upper right abdomen.
Swelling of the spleen, called splenomegaly.
Bone, muscle or joint pain.
Swollen feet and ankles.
Buildup of fluid in the abdomen due to liver failure, called ascites
treatment: Ursodeoxycholic acid (UDCA) is the main treatment for PBC. It can help delay liver damage in most people, particularly if you start taking it in the early stages of the condition.
Primary Sclerosing Cholangitis (PSC) is a biliary disease. Define PSC, it’s symptoms + treatment
Primary sclerosing cholangitis (PSC) is a chronic liver disease in which the bile ducts inside and outside the liver become inflamed and scarred and eventually narrowed or blocked
symptoms;
often asymptomatic! But symptoms include; pain in the abdomen, itchy skin, diarrhea, jaundice, feeling tired or weak, and fever.
treatment:
surgery or liver transplant depending on extent of damage
define pruritis
pruritis= severe itching of skin
name the common clinical signs of chronic liver disease
- palmar erythema (red palms of hands)
-gynaecomastia (enlarged breasts in males)
-hair loss
-spider naevi (a cluster of minute red blood vessels visible under the skin)
-leuchonychia (white nails)
-clubbing of nails
-proximal wasting
-scratch marks (because they scratch the pruritis)
-xanthelasma (yellow bumps on or around eyelid)
what conditions of the spleen can cause a low platelet count
hyposplenism or splenomegaly can cause low platelet count
think of the spleen as a giant macrophage that consumes platelets= less function of spleen =less platelets
explain the mechanism of ascites (accumulation of fluid in the peritoneal cavity, is commonly associated with liver cirrhosis but can also be caused by heart failure, kidney disease, or malignancies)
Portal hypertension → increases fluid leakage into the peritoneum.
Reduced effective blood volume → triggers RAAS activation.
RAAS activation → increases aldosterone, promoting sodium and water retention.
Sodium and water retention → worsens ascites by increasing plasma volume and portal pressure, driving more fluid into the abdominal cavity.
The Child-Pugh score is used to class patients with liver cirrhosis into decompensated and compensated cirrhosis. Explain the difference between compensated and decompensated cirrhosis with reference to Child-Pugh score
Compensated Cirrhosis: (Child-Pugh score 5-6) The liver can still perform most of its functions despite scarring. Patients may have few or no symptoms. Portal hypertension is typically mild.
Decompensated Cirrhosis: (Child-Pugh score 7 and above) The liver can no longer compensate, leading to portal hypertension, ascites, jaundice, variceal bleeding, and hepatic encephalopathy.
what is NAFLD (non-alcoholic fatty liver disease) now known as?
NAFLD is now known as Metabolic dysfunction-associated steatotic liver disease (MASLD)
patients with type 2 diabetes insulin resistance are more likely to have Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously known as NAFLD). Explain the mechanism behind why these patients are more likely to suffer from fatty liver
Insulin resistance leads to increased free fatty acids from adipose tissue, which accumulate in the liver. This increased glucose activates ChREBP
De novo lipogenesis (SREBP1) in the liver increases fat production due to high insulin and glucose levels. This inhibits IR tyrosine kinase. Inappropriate gluconeogenesis (FOXO1-MEDIATED). Impaired glycogen synthesis (muscle and liver)= Akt2-mediated
Impaired fat export as VLDL leads to lipid build-up within hepatocytes as lipolysis is impaired. This all induces PPAR-gamma (which is lipogenic= fatty liver)
this all causes oxidative stress and inflammation from excess fat and high blood sugar further damage liver cells.
Altered adipokine and cytokine profiles promote liver fat accumulation and inflammation.
explain (simply) how most of alcohol is broken down
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.
what gene is responsible for asian flush?
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
what is the HPA stress response? n.b. when a person is hangover this response kicks in
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.
The human body metabolizes alcohol primarily through three main pathways:
1) Alcohol Dehydrogenase (ADH) Pathway (Primary pathway)
2) Microsomal Ethanol-Oxidizing System (MEOS)
3) Catalase Pathway
explain each one
- 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.
- 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.
- 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.
what metabolite of ethanol contributes to the symptoms of a hangover
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
how does ethanol interact with GABA
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
explain why drunk (alcohol intoxicated people) experience ataxia, dysmetria, nystagmus, delayed reaction time, nausea/vomiting, memory problems, pain relief, mood alteration, addiction
n.b. Dysmetria (English: wrong length) is a lack of coordination of movement typified by the undershoot or overshoot of intended position with the hand, arm, leg, or eye. It is a type of ataxia. It can also include an inability to judge distance or scale
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
name 6 neuropsychological effects of chronic consumption of alcohol– alcohol use disorder
- 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
what is atrophy
atrophy= decrease in size
what is beriberi
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)
what are some features of fetal alcohol syndrome (FAS)
- 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
what is a melaena stool and its cause
Melaena refers to black, tar-like, sticky stools and usually results from upper gastrointestinal bleeding
the acronym SOCRATES is used to understand the pain a patient is going through. Name each one.
Site
Onset
Character,
Radiation,
associated features, Time course, Exacerbating or alleviating factors, Severity
what signs are there in addition to sharp, sudden onset chest pain if a patient is having an aortic dissection?
- pain in jaw
-abdominal pain
-tearing pain in the back
-syncope
what are the causes of lichen planus
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.
what is diverticulitis and its symptoms
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.
what is claudicatio/claudication
Claudication is pain in the legs or arms that occurs while walking or using the arms
What clinical signs might you find in a patient with pancreatitis?
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)
what is the difference between grey turner’s sign and cullen’s sign and what do they each indicate
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
What symptoms might patients with pancreatitis report?
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
Your consultant asks you if the patient was tender over the McBurney point. Where is the McBurney point located and what might tenderness in this region indicate?
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
What is the Rovsing’s sign?
Rovsing’s sign= Palpation of the left lower quadrant increases the pain felt in the right lower quadrant
What could be clinical signs of a ruptured ectopic pregnancy?
Severe unilateral pelvic pain
vaginal bleeding
Referred pain to the shoulder
fainting
what is pretibial myxoedema a sign of
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)
What might be symptoms of pelvic inflammatory disease?
Vaginal discharge
Fever
Dyspareunia (painful sexual intercourse)
Pelvic pain
what is a positive murphys sign?
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
The pictures show: Erythema Nodosum(painful patches of skin that look red or darker than the surrounding skin), Angular Cheilitis and Aphthous Ulceration (lil white ulcer in mouth). Can you name an underlying illness that might be associated with all these presentations in a patient who also suffers from intermittent diarrhoea and abdominal pain? Pick the most likely answer!
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.
Why would you assess the fluid thrill in an abdominal examination?
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.
Explain the epidemiology of Hepatitis A Virus (HAV)
Transmission: Fecal-oral route.
Incubation: 2–6 weeks.
Does NOT cause a carrier state or chronic infection.
Explain the epidemiology of Hepatitis B Virus (HBV)
Transmission: Parenteral, sexual, perinatal.
Incubation: 4–20 weeks.
Carrier state and chronic hepatitis possible (5–10% in adults, higher in neonates).
Explain the epidemiology of Hepatitis C Virus (HCV)
Transmission: Parenteral (IV drug use, transfusions).
Incubation: 2–26 weeks.
Chronicity (=long-lasting disease) is very common (~80%).
1) Explain the epidemiology of Hepatitis D Virus (delta virus/HDV)
2) Differentiate between coinfection and superinfection (HDV)
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.
