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Chronic kidney disease:

slow, progressive loss of kidney function lasting at least 3 months/ involves evidence of kidney damage or reduced kidney function

Chronic kidney disease key features:

-          Progressive nephron loss

-          Often undetected until kidney function falls below 25%

-          Waste products and fluid accumulate in body

-          May progress to kidney failure

CKD stats

-          1/10 Australian adults

-          Contributes to 1/9 deaths

CKD co-morbidities

-          Cardiovascular disease

-          Type 2 diabetes

CKD risk factors:

-          Obesity

-          Physical inactivity

-          Poor diet

-          Smoking

-          Hypertension

-          Family history

-          Indigenous Australian

Stage 1 of CKD:

-          1: kidney damage w normal function/ GFR: >90mL/min

Stage 2 of CKD:

-          2: mild loss of function / GFR: 60-89mL/min

Stage 3 of CKD:

-          3: moderate loss/ GFR: 30-59mL/min

Stage 4 of CKD

-          4: severe loss/ GFR: 15-29Ml/min

Stage 5 of CKD

-          5: kidney failure/ GFR: <15mL/min

CKD Diagnosis requirements:

-          kidney damage for over 3 months

-          Declining GFR

-          Albuminuria/proteinuria

-          Abnormal biopsy findings

Causes of CKD:

-          Glomerulonephritis

-          Chronic infections

-          Congenital abnormalities

-          Hypertension

-          Urinary obstructions

-          Collagen disease (Lupus)

-          Nephrotoxic drugs

-          Diabetes

CKD Disease process:

1.      Damage nephron

2.      Adaptive hyper filtration

3.      Inc. glomerular permeability & Inc renin angiotensin aldosterone system

4.      Increase in filtration of proteins and macromolecules

5.      Hypertension

6.      Inflammation of the glomerulus and tubules

7.      Fibrosis and sclerosis of the glomerulus and tubules

8.      Dec. GFR/ Dec. urine output/ systemic complications

CKD Effects of hypertension

-          Damages blood vessels

-          Reduces kidney blood supply

-          Damages glomeruli

-          Causes focal segmental sclerosis and nephrosclerosis

Glomerulonephritis:

inflammation of the glomeruli

Post strep Glomerulonephritis:

-          Type 3 hypersensitivity

-          Antibodies form immune complexes

-          Complexes deposit in glomeruli

-          Complement proteins trigger inflammation

-          Immune cells damage glomeruli

Complications of CKD:

1.      Uraemia: waste products accumulate in blood

2.      Anaemia: reduced erythropoietin production by kidneys

3.       Fluid retention and oedema:  sodium and water retention

4.      Electrolyte imbalance: hyperkalaemia, hypocalcaemia

5.      Bone disease: low calcium stimulates excess parathyroid hormone release

CKD General symptoms:

-          Fatigue

-          Weakness

-          Malaise

-          Reduced exercise tolerance

CKD Urinary symptoms:

-          Frequent urination

-          Nocturia (urinating At night)

-          Difficulty urinating

GFR:

glomerular filtration rate

Proteinuria:

protein in urine

Uraemia

-          build up of toxins in blood

Hyperkalaemia:

-          high potassium

Hypocalcaemia:

low calcium

Nephrosclerosis:

hardening of nephrons

Oedema:

: fluid swelling

Liver

metabolic and regulatory functions are carried out by specialised cells hepatocytes

Liver key functions:

-          Metabolism: processes carbs, proteins, fats, hormones etc.

-          Synthesis: production of plasma proteins, clotting factors, cholesterol, glucose, bile, amino acids and urea

-          Storage: stores glycogen and fat-soluble vitamins

-          Blood sugar regulation

-          Immunity

Liver failure:

extensive parts of the liver are damaged beyond repair and can no longer function  correctly.

Acute liver failure

rare, rapid onset and symptoms do not exceed 6 months

-          Pathology: hepatocyte inflammation or damage

-          Severe cases: high mortality rare

-          Causes: poising from mushrooms or drug overdose

Chronic liver failure:

much more common, develops gradually over months/years, w symptoms more than 6 months

-          Pathology: longstanding hepatocyte damage that triggers permanent structural changes

-          Causes: long term alcohol use, other chronic conditions

Causes of liver disease:

-          Alcohol consumption

-          Viral infections: Hepatitis B, C & D

-          Non alcoholic fatty liver disease (NAFLD): accumulation of triglycerides w hepatocytes

-          Medicines

-          Inherited disorders

-          Autoimmune diseases

-          Malignant tumours

-          Structural abnormalities

Liver disease pathology

1. Inflammation and steatosis

2. fibrosis

3. cirrhosis

4. end of stage liver failure

Liver disease pathology 1 :Inflammation and steatosis

inflammatory changes (hepatitis) and fatty accumulation (steatosis), liver may be tender or asymptomatic, stage is usually reversible, liver can still regenerate if cause is removed

Liver disease pathology 2:Fibrosis

chronic, untreated inflammation triggers hepatocyte necrosis, immune cells release cytokines and growth factors that activate hepatic stellate cells/ Non-functional CT builds up, disrupting healthy blood flow

Liver disease pathology 3: Cirrhosis

severe, extensive fibrosis that permanently alters the liver. Healthy cells replaced by scar tissue and smooth tissue> nodular/ blood flow is deeply compromised, diminishing overall function

Liver disease pathology 4: End stage liver failure

features multi system complications & only transplant can cure

Liver disease early symptoms

-          Nausea

-          Loss appetite

-          Fatigue

-          Diarrhea

Liver disease common symptoms

-          Jaundice

-          Pale stools

-          Dark urine

-          Bruising and bleeding

-          Portal hypertension

-          Ascites

-          Pruritus (itching)

-          Hepatic encephalopathy (HE): reduced concentration, confusion, sleep disturbance

-          Gynaecomastia & red. Fertility

Major liver failure complications

-          Cerebral oedema: excessive fluid accumulation in brain

-          GI bleeding: results from severe lack of clotting factors

-          Infections: impaired immunity> susceptibility to systemic infections eg sepsis, pneumonia and UTI

-          Kidney failure: frequently flows liver failure, cases of acetaminophen overdoses

Peptic ulcer

open sores that develop in stomach lining (gastric ulcers) or the duodenum ( duodenal ulcers), commonly caused by H.pylori infection.

Peptic ulcer H. pylori:

-          damages protective mucus layer

-          increases stomach acid

-          irritates stomach lining

-          responsible fot most duodenal ulcers, ~60% stomach ulcers

 

H.pylori mechanism:

-          uses flagella to move thru mucous

-          Produces urease enzyme

-          Converts urea to ammonia + carbon dioxide

-          Ammonia neutralises acid and protects bacteria

Causes of peptic ulcers

• H. pylori

• NSAID USE:

  -          other cause of PU

  -          eg aspirin or ibuprofen

  -          reduce protective chemicals in stomach lining

PU - other risk factors:

-          smoking

-          alcohol

-          stress

-          spicy foods

-          steroids

-          anticoagulants

-          SSRIS

GI tract layers:

1.      epithelium

2.      lamina propria

3.      muscularis mucosa

Gastric cells:

-          mucous cells> mucous

-          parietal cells> hydrochloric acid

-          chief cells> pepsinogen

PU symptoms

-          burning stomach pain

-          indigestion

-          bloating

-          nausea

-          pain worse on empty stomach

-          pain at night

-          weight loss

-          vomiting

-          black/ tarry stools

-          vomiting blood

PU complications

-          Internal bleeding: bloody vomit, anameia, fainting, can be fatal

-          Perforation (hole): can cause peritonitis, medical emergency

-          Obstruction: food cannot pass normally, weight loss

IBD

conditions where intestines become inflamed

Crohn’s Disease:

-          Effect any part of GI tract

-          Most commonly effects distal small intestine and proximal colon

-          Inflammation is transmural (full thickness)

-          Has skip lesions (normal tissue between diseased areas

-          Produces cobblestone appearance

-          Causes fibrosis> narrowing (stenosis) > bowel obstruction

Crohn’s Disease symptoms

-          Diarrhea

-          Abdominal pain

-          Fever

-          Anaemia

-          Malnutrition/ malabsorption

-          Fissures

-          Fistulae

-          Abdominal abscesses

-          Skin tags

Crohn’s Disease Extra-intestinal manifestations

-          Arthritis

-          Skin problems liver disease

-          Kidney stones

-          Eye inflammation

Ulcerative colitis:

-          Limited to the colon and rectum

-          Inflammation only affects the inner mucosal lining

-          Begins near the anus and spreads upward continuously

-          No skip lesions

Ulcerative colitis symptoms

-          Rectal bleeding

-          Diarrhea

-          Cramping abdominal pain

-          Anaemia

-          Constipation

Ulcerative colitis Extra-intestinal manifestations

-          Fever

-          Joint inflammation

-          Eye inflammation

-          Mouth ulcers

-          Tender nodules

Pathogenesis of IBD:

-          Increased risk w family history

-          Linked to MHC class 2 mutations

-          Cytokines/ interleukins may contribute

Immunological factors IBD:

-          Abnormal immune response

-          Possible reaction to intestinal self-antigens or bacterial antigens

-          Helper t cells may damage tissue

-          Chronic inflammation develops

Environmental triggers IBD:

-          Viruss/ bacteria

-          Smoking (inc. crohns, red. UC)

-          Diet

-          Antibiotics