PATHOPHYSIOLOGY

UNIT-4

SYLLABUS

• Inflammatory Bowel disease, Jaundice, Hepatitis (A, B, C, D, E, F), Alcoholic liver disease.
• Disease of Bones and Joints: Rheumatoid Arthritis, Osteoporosis, Gout.
• Principles of Cancer: Classification, etiology and pathogenesis of cancer.

INFLAMMATORY BOWEL DISEASE

• These are group of disease which develop due to chronic inflammation of GIT (mostly occurs in intestines).
• Not able to digest food, absorb nutrition and eliminate waste.
• It is of two types:
  1. Crohn's disease
  2. Ulcerative Colitis

1. Crohn's disease

• It is a condition in which inflammation occurs in any part of GIT.
• It mainly starts from the end point of small intestine. (ileum) and forms skipping lesions. (appear in patches)

2. Ulcerative disease

• It is a chronic/long term condition in which inflammation occurs in large intestine, which mainly starts from colon rectum and this is continuous lesions.
• In this, the colon becomes inflamed and ulcers develop on the lining of colons (in severe case). These ulcers bleed and produce pus & MUCUS.

ETIOLOGY

• The exact causes are not known. But it can be caused due to:
• Genetic factors / predisposition
• GIT immune system
• Lymphatic obstructions
• Infections $\rightarrow$ Mycobacterium paratuberculosis, infective diarrhoea, enteric microflora.
• Environmental factors $\rightarrow$ Diet, stress, Allergies, smoking, Antibiotics etc.
• Fat intake, fast food, milk and fiber consumption.

PATHOGENESIS

SIGN AND SYMPTOMS

• Chronic diarrhoea
• Weight loss
• fever
• Pain in abdomen
• Rectal bleeding
• fatique
• Anaemia
• Dehydration

COMPLICATIONS

• Bleeding
• Severe dehydration
• Colon cancer
• Bowel obstruction
• ulcers
• fistula
• Anal fissure

TREATMENTS

• $\uparrow$ Quality of life
• Avoid smoking, stress etc...
• Surgery (when no choice)
• Medications (Antibiotics, Immunomodulators)

JAUNDICE

• It is defined as, it is the condition of yellowing of skin, mucous and sclera of the eye due to accumulation/deposition of bilirubin (Bile pigments).
• It is occurs due to condition of Hyperbilirubinemia i.e. increases level of bilirubin.

ETIOLOGY

These factors can be classified on the basis of their types:

• 1. Pre-Hepatic Jaundice: It is hemolytic Jaundice which occurs when the level of bilirubin increases due to breakdown and destruction of RBC (Hemolysis).

• It is caused due to hemolytic anemia, malaria, thalassemia, toxins etc.

• 2. Hepatic Jaundice: It is occured due to defected liver cells or impaired functions of liver, when liver fails to metabolise/excrete bilirubin. Etiology $\rightarrow$ Due to viral infections (Hepatitis A, B, C), tuberculosis, yellow fever, Alcohol, shock.

• 3. Post-Hepatic Jaundice: It is occured due to obstruction of biliary duct (blockage) which interrupt the flow of bile. It is caused due to Biliary atresia, gallstone in duct etc.

• 4. Neonatal Jaundice: It occurs in neonates.

SIGN AND SYMPTOMS

• Yellowing of skin and sclera of eyes
• weakness
• Gastrointestinal bleeding
• Diarrhoea
• Anemia
• Oedema
• weight loss
• itching of skin
• Dark Coloured urine
• fatigue
• Abdominal pain

PATHOGENESIS

TREATMENTS

• A high water intake and low diet of fact, helps to treat jaundice.
• Prevent breakdown/destruction of RBCs.
• Prevent further liver damage.

COMPLICATIONS

• Anemia
• Bleeding
• Electrolyte abnormalities
• Infections
• Liver cirrhosis
• Cancer
• Chronic hepatitis

HEPATITIS

• It is a condition of liver inflammation, which occurs due to any type of injury/infections.
• It is mostly caused due to viral hepatitis (hepatitis viral infections), toxic substances (alcohol, certain drugs) and autoimmune diseases.

TYPES

• Hepatitis A

• It is communicable liver disease which is caused by hepatitis A virus (single stranded RNA virus).

• It can be transmitted via faecal-oral routes by consuming contaminated food or water.

• Hepatitis B

• It is a serious liver infection which is caused by infection of hepatitis B virus (double shelled spherical DNA virus).

• This infection becomes chronic lasting for 6 months and more and mostly affects the infants and children and increases risk of liver failure, liver cancer or liver cirrhosis.

• It is one of the sexually transmitted disease (STD) and it can be transmitted through contaminated needles, mother to infants, sex, close contact, blood transfusion and in hospitals.

• Hepatitis C

• It is liver inflammation or serious liver damage which is caused by infection of Hepatitis C Virus (Single stranded enveloped RNA virus).

• It can be caused/spread through contaminated blood, blood transfusion, contaminated needles. It may cause liver cirrhosis, liver cancer or Liver failure.

• Hepatitis D:

• It is a liver disease which present in both acute/chronic forms and it is caused by infections of hepatitis D virus (small single stranded RNA virus) Delta virus.

• It is self-replicating defective RNA virus, and only a person who is already infected with Hep-B can become infected with Hepatitis-D.

• It can be spread through contaminated needles, blood transfusion, sex etc. Vaccination against hepatitis B is only method to prevent hep-D infections.

• Hepatitis E:

• It is a liver infection caused by infection of Hepatitis E Virus (small, single stranded, non-enveloped RNA virus).

• It is spread through faecal-oral route, contaminated water supply and food supply, poor sanitation.

• Hepatitis F:

• It is also known as hypothetical virus.

• It is non-existent, rounded, virus-like particles, and which is caused by infections of hepatitis virus.

SIGN AND SYMPTOMS

• fatique
• Nausea and vomiting
• Pain
• fever
• Appetite loss
• weight loss
• weakness
• Dark coloured urine

COMPLICATIONS

• Liver damage/failure
• Liver Cirrhosis (liver scarring $\rightarrow$ improper liver functions)
• Liver cancer etc.

TREATMENTS

• No proper treatments.
• Vaccination for virus.
• Medications - acc to its types.
• Healthy diets, prevents risk factors.

ALCOHOLIC LIVER DISEASE

• It is a condition of a structural and functional changes in the liver which is mostly caused due to excessive consumption of alcohols.
• It is divided into three stages:

  1. Alcoholic fatty liver : It is the initial and mildest stage which is caused by prolonged consumption of small amount of alcohols.

  2. Alcoholic hepatitis : It is the second stage which is caused due to excessive consumption of alcohol which increases fatty changes and liver cell necrosis.

  3. Alcoholic cirrhosis : It is the third and most advanced stage, which obstructs liver function and reduces blood flow through liver. Degeneration of cells, inflammation and fibrous thickening of tissue.

ETIOLOGY

• It is caused due to prolonged excessive consumption of alcohol (heavy drinking) resulting in Cirrhosis of liver tissue.
• It is mostly depends on how long alcohol consumed.

SIGN AND SYMPTOMS

• Initially, there are no symptoms but it become severe after prolonged heavy drinking.
  • fatique and loss of energy
  • Apetite and weight loss
  • Nausea
  • Pain in abdomen
• At advance stage
  • Oedema and ascites
  • Jaundice
  • Redness on palms
  • Impotence, shrinking of testicles, enlarged breasts in men etc.

PATHOGENESIS

COMPLICATIONS

• Ascites (abdominal swelling) and bacterial peritonitis
• Coagulopathy (bleeding disorders)
• Hypertension
• kidney failure
• Liver cancer / failure

TREATMENTS

• Less consumption of alcohol
• Healthy diet (low salt)
• vaccination for influenza, hepatitis A, B, pneumonia
• Antibiotics
• Surgery
• Liver transplant

DISEASE OF BONES & JOINTS

• These are those disease which are related to bones and Joints. Osteology is the study of bones and teeth.
• Joints are those sites where two or more than two bones are meet/join together to carry out the movement.
• Three main disease:
  1. Rheumatoid arthritis
  2. Osteoporosis
  3. Gout

RHEUMATOID ARTHRITIS

• It is chronic, inflammatory, autoimmune disorder which affects the wide range of Joints, connective tissue, tendons etc.

• It is autoimmune disorder, so immune system attacks the synovium.
• due to this, synovium becomes inflamed and thickens which ultimately destroys the cartilage and bone within Joints. (weak swollen and painful Joints).
• Synovitis (inflammation in Synovium $\rightarrow$ lining of membrane of Joints) $\rightarrow$ growth of tiny Inflammatory cells $\rightarrow$ Bone erosion.

ETIOLOGY

• Womens are more susceptible than mans.
• Genetic factors $\rightarrow$ Genes connected to Immune responses (HLA-A, HLA-B proteins). HLA-C, HLA-D. Other genes PTPN 22, PADI4, STAT4 etc.
• Environmental factors $\rightarrow$ Smoking, Pollutants, Obesity.
• Bacterial and viral pathogens (eg. sarcoidosis).

PATHOGENESIS

• Various etiological factors $\rightarrow$ Inflammation $\downarrow$
• Activation of T-cells and B-cells $\downarrow$
• Production of autoantibodies and cytokines $\downarrow$
• Overproduction of pro-inflammatory cytokines including TNF-$\alpha$ and IL-6, IL-1 $\downarrow$
• Inflammatory pathway initiated in joints $\downarrow$
• proliferation of synovial cells $\downarrow$
• Pannus formation $\downarrow$
• level of lipids in synovial membrane increased $\downarrow$
• Cartilage destruction and Bony erosion $\downarrow$
• Rheumatoid Arthritis (inflammation in joints)

SYMPTOMS

• Pain and stiffness in joints (in wrists)
• Swelling
• Deformity of joints
• fatique, weakness
• Depression

COMPLICATIONS

• Osteoporosis
• Dry eyes & mouth
• Infections
• Heart problems
• Lung disease
• lymphoma (risk of blood cancer in lymph system)

TREATMENTS

• Healthy diet
• $\uparrow$ Physical exercise
• Surgery.
• Medications $\rightarrow$ Methotrexate, anti TNF agents, corticosteroids etc.

OSTEOPOROSIS

• Osteo $\rightarrow$ Bones & Porosis $\rightarrow$ Pores
• It is a condition in which bones become weak and brittle.
• In this condition, the density and strength of bones are decreases which results in fragile bone. (Bones become porous).

• It is caused due to Imbalance between new bone formation and old bone resorption.

ETIOLOGY

• Age (more in older age)
• Deficiency of oestrogen in females
• deficiency of androgen in males
• inadequate intake of calcium and Vit. D
• Thyroid disorders, Genetic disorders, Bone cancer etc.

SIGN AND SYMPTOMS

• No symptoms at early stage, but after this
• Back pain due to fractured/collapsed vertebra
• Easy bone fractures
• Loss of height over time
• A stooped posture

COMPLICATIONS

• Hip fractures on even small accident / easily by falling.
• Spinal fractures occur even without any accident.
• Back pain, Lost height, A stooped posture.

PATHOGENESIS

TREATMENTS

• Healthy life style
• Stop alcohol/smoking
• Calcium/vit.D Supplements to prevents
• Medications $\rightarrow$ Raloxifene (effect similar to estrogen). Hormone related therapy. Monoclonal antibody.

GOUT

• It is a metabolic disorder occurs due to deposition of monosodium urate (uric acid) within the tissue, leads to the inflammation and pain (mostly in Joints).
• It is Inflammatory disease and a very painful form of arthritis due to deposition of uric acid crystals due to hyperuricemia (elevated levels of uric acid in blood).

TYPES

• Primary Gout: It is mostly occurs due to unknown reasons/results.
• Secondary Gout: It is mostly caused due to underlying disease.

ETIOLOGY

• It is caused due to overproduction of uric acid (Hyperuricemia).
• Genetic factors (mutation in genes involves purine metabolism).
• Underlying disease (hypertension, diabetes mellitus, obesity, renal disease, Sickle cell anemia, chronic kidney disease).
• Other drugs $\rightarrow$ Cytotoxics, thiazides, hydrochlorothiazides etc.
• $\uparrow$ purine intake (Red meat, sea food, high fructose).

SIGN AND SYMPTOMS

• Joint pain (mostly at night)
• Redness, swollen, Inflammation
• Gout attack (severe pain)
• formation of tophi (large, hard nodules formed due to deposition of urate crystals in soft tissue).

PATHOGENESIS

COMPLICATIONS

• Disability in patients due to chronic gout
• formation of tophi
• Hypertension
• Urate kidney stone
• Albuminuria

TREATMENTS

• Healthy lifestyle / ideal weight
• Avoids purines rich foods
• Increasing fluid intake
• $\downarrow$ Alcohol consumption
• Medications $\rightarrow$ Colchicine, Corticosteroids, Probenecid, NSAIDs (Indomethacin, diclofenac etc.), Allopurinols etc.

CANCER

• It is a group of disease which involve an abnormal and uncontrolled cell division in body cells.

• Neoplasm: An abnormal mass of tissue that forms when cells grow and divide more than they should or do not die when they should, it leads to formation of tumour, develop cancer.

• It is of two types:

1. Benign: It is not a cancer (initial) and in this tumour develops in localised and do not spread to other body parts. (Can treat).

2. Malignant: It is a cancer which grow rapidly and also spread to other body parts. It is dangerous & leads to death. (no treatment).

• Metastasise: It is a process in which the tumour spreads to other sites from the origin.

• Carcinogenesis / Tumourigenesis: It is a multistep process which begins with conversion of normal cells into cancer cells.

ETIOLOGY

• Mutation in genes
• Heredity (from parents)
• Virus, Bacteria etc.
• Physical Agents $\rightarrow$ Carcinogens, Radiations (UV rays etc) etc.
• Chemical Agents $\rightarrow$ some toxic substances (eg. Benzene), plastic.
• Others $\rightarrow$ Smoking, Tobacco, Air pollution, Diet, Alcohols, obesity, hormones etc.

TYPES

It can be classified as many way, it is mainly based on where it begins:

• Carcinomas: It begins in the Skin or the tissue that covers the surface of internal organs and glands. eg. Breast cancer, Prostate cancer, Lung cancer, Colorectal cancer etc.
• Sarcomas: It begins in the tissue that support and connects the body. A sarcoma can develop in fat, muscles, nerves, tendons, joints, blood vessels, Lymph vessels, cartilage/bones.
• Leukemias: It is blood cancer which begins when healthy blood cells change and grow uncontrollably.
• Lymphomas: It begins in the lymphatic system (helps to fight against infections).

SIGN AND SYMPTOMS

• $\downarrow$ Normal functions/work
• Shortness of breath
• Chest pain
• Cough
• Abdominal pain
• Heaviness
• Severe pain
• Anaemia
• Anorexia
• weight loss (changes)
• Sleeping disorder
• fatique

PATHOPHYSIOLOGY / PATHOGENESIS

COMPLICATIONS

• Weight loss
• Constipation
• confusion
• excessive thirst
• frequent urination
• Hormonal Imbalance
• Nervous System problem
• Breathing problem
• Death at last

TREATMENTS

• Radiotherapy: Burns that tumour (also burn some sideway cells).
• Surgery: Cut the tumor (most dangerous).
• Chemotherapy: through chemicals & medicines. e.g. Mechlorethamine, Mercaptopurines, Cisplatin and other antibiotics.