Kidney Functions and Processes

Kidney Function

• Kidneys excrete waste, including dental drugs
• Regulate fluid volume and acid/base
• Maintain blood pressure
• Synthesize erythropoietin, renin, and 1.25 cholecalciferol
• Act as a target organ for parathormone, aldosterone, and ADH

Glomerular Filtration Rate (GFR)

• Normal GFR: 100ml/min (150L/day)
• Reabsorption rate: 99% of liquid

Urine Production

• Normal urine production rate: 0.5-1.5 ml/kg/hr
• Unreabsorbed liquid contains: urea, creatinine, K+, NH4, H+, PO4, hormones, and drugs

Kidney Disease

• Patients are often asymptomatic until advanced disease
• 40% of people with kidney disease are unaware
• Risk factors: hypertension, diabetes, Asian and Black Caribbean ethnicity

Chronic Kidney Disease Risk Factors

• Diabetes
• High blood pressure
• Heart problems or stroke
• Obesity
• Family history
• Tobacco use
• 60+ years old

Kidney Disease Stages

• Stage 1: Kidney damage, normal function
• Stage 2: Kidney damage, mild loss of function
• Stage 3: Moderate to severe loss of function
• Stage 4: Severe loss of function
• Stage 5: Kidney failure, requiring treatment to live

Risks for Dental Treatment

• Stages 4 and 5 pose a risk for dental treatment
• GFR < 30 in these stages

Consequences of Kidney Disease

• Increased cardiovascular risk
• Anaemia and reduced immunity due to high urate levels
• Increased risk of bleeding
• Fluid imbalance
• Decreased bone health
• Buildup of toxins
• Reduced drug excretion

Dental Implications of Kidney Disease

• Increased periodontal disease
• Oral signs of anaemia (e.g., angular chelitis, esophageal web)
• Bone abnormalities
• Potential increased bleeding tendency
• Care with ibuprofen (NSAIDs)
• Good oral health supports nutrition/preparation for transplant

Jaw Bone Changes in Chronic Kidney Disease

• Failure to excrete PO4 and low levels of active Vitamin D
• Low free Ca2+ levels
• Increased parathormone release
• Osteoclastic activity
• Formation of a central giant cell granuloma

Drug Alterations in Chronic Kidney Disease

• No alteration required: lignocaine, articaine
• Dose alteration required: amoxycillin (reduce dose if GFR < 10), NSAIDs (avoid if GFR < 10 or with diabetes), erythromycin (avoid due to drug interactions), midazolam (use with caution if stage 4+, GFR < 30)

Dialysis

• Types: haemodialysis, peritoneal dialysis
• Necessary introduction: when function is no longer able to meet demand (GFR < 30)

Kidney Function

• Kidneys excrete waste, including dental drugs
• Regulate fluid volume and acid/base
• Maintain blood pressure
• Synthesize erythropoietin, renin, and 1.25 cholecalciferol
• Act as a target organ for parathormone, aldosterone, and ADH

Glomerular Filtration Rate (GFR)

• Normal GFR: 100ml/min (150L/day)
• Reabsorption rate: 99% of liquid

Urine Production

• Normal urine production rate: 0.5-1.5 ml/kg/hr
• Unreabsorbed liquid contains: urea, creatinine, K+, NH4, H+, PO4, hormones, and drugs

Kidney Disease

• Patients are often asymptomatic until advanced disease
• 40% of people with kidney disease are unaware
• Risk factors: hypertension, diabetes, Asian and Black Caribbean ethnicity

Chronic Kidney Disease Risk Factors

• Diabetes
• High blood pressure
• Heart problems or stroke
• Obesity
• Family history
• Tobacco use
• 60+ years old

Kidney Disease Stages

• Stage 1: Kidney damage, normal function
• Stage 2: Kidney damage, mild loss of function
• Stage 3: Moderate to severe loss of function
• Stage 4: Severe loss of function
• Stage 5: Kidney failure, requiring treatment to live

Risks for Dental Treatment

• Stages 4 and 5 pose a risk for dental treatment
• GFR < 30 in these stages

Consequences of Kidney Disease

• Increased cardiovascular risk
• Anaemia and reduced immunity due to high urate levels
• Increased risk of bleeding
• Fluid imbalance
• Decreased bone health
• Buildup of toxins
• Reduced drug excretion

Dental Implications of Kidney Disease

• Increased periodontal disease
• Oral signs of anaemia (e.g., angular chelitis, esophageal web)
• Bone abnormalities
• Potential increased bleeding tendency
• Care with ibuprofen (NSAIDs)
• Good oral health supports nutrition/preparation for transplant

Jaw Bone Changes in Chronic Kidney Disease

• Failure to excrete PO4 and low levels of active Vitamin D
• Low free Ca2+ levels
• Increased parathormone release
• Osteoclastic activity
• Formation of a central giant cell granuloma

Drug Alterations in Chronic Kidney Disease

• No alteration required: lignocaine, articaine
• Dose alteration required: amoxycillin (reduce dose if GFR < 10), NSAIDs (avoid if GFR < 10 or with diabetes), erythromycin (avoid due to drug interactions), midazolam (use with caution if stage 4+, GFR < 30)

Dialysis

• Types: haemodialysis, peritoneal dialysis
• Necessary introduction: when function is no longer able to meet demand (GFR < 30)

Pathogenicity and Virulence

• Pathogenicity: The ability to cause disease
• Virulence: The degree of pathogenicity
• Virulence factor/gene: A gene that drives the pathogenesis of an organism
• Housekeeping gene: A gene involved in all aspects of a bacterium's life, such as metabolism, protein synthesis

Koch's Postulates

• Determine if a microbe is pathogenic
• 3 Postulates:
  • 1. Pathogen occurs in every case of the disease and distribution corresponds to that of lesions observed
  • 2. Pathogen does not occur in healthy subjects
  • 3. After isolation and repeated growth in pure culture, pathogen can induce disease in susceptible animals

Anomalies to Koch's Postulates

• HIV: Can't grow in culture, poor animal model
• Helicobacter pylori: Carriage doesn't necessarily mean disease, no good animal model
• Streptococcus mutans: Not the only cause of caries, sometimes no disease
• Chlamydia: Can't grow in separate culture
• Cholera: Poor animal models, but eventually shown
• Diptheria: Disease throughout body, but bacteria only in throat
• TB: Carried asymptomatically in 1/3 people

Molecular Koch's Postulates

• 3 Postulates:
  • 1. Phenotype should be associated significantly more often with pathogenic organism than with non-pathogenic member or strain
  • 2. Specific inactivation of gene associated with the suspected virulence trait should lead to a measurable decrease in virulence
  • 3. Restoration of full pathogenicity should accompany replacement of the mutated gene with the wild type original

Virulence Genes and Pathogenicity Factors

• Virulence gene: Causes disease, often encoded on mobile genetic elements
• Origins of virulence genes:
  • 1. Plasmids (adhesin genes, antibiotic resistance genes, toxin genes)
  • 2. Bacteriophages (toxin genes)
  • 3. Pathogenicity islands (toxin gene systems)
• 4 Bacterial pathogenicity factors:
  • 1. Transmission
  • 2. Adherence (epithelium, skin, etc.)
  • 3. Invasiveness (sometimes into cells)
  • 4. Ability to cause damage (cause pathology)

Transmission and Adherence

• 3 Methods of transmission:
  • 1. Inhalation
  • 2. Ingestion (faecal contamination)
  • 3. Inoculation (contaminated needles and blood transfusions, skin contact, insects, sexual contact)
• 3 Ways microbes adhere:
  • 1. Flagellae (also for motility)
  • 2. Fimbriae (pili) - enable microbes to bind to the cell wall
  • 3. Specialised surface proteins (direct attachment, signalling to the eukaryotic cell)

Bacterial Burden and Colonization

• Difference between colonization and infection:
  • Colonization: Presence of microbes without accompanying disease
  • Infection: Presence of microbes resulting in disease
• 4 Stages of bacterial burden:
  • 1. Contamination
  • 2. Colonization
  • 3. Critical colonization
  • 4. Infection

Microbial Survival

• 3 Ways microbes survive:
  • 1. Affect host function
  • 2. Immune evasion (antigenic shift, e.g. Neisseria, Borrelia)
  • 3. Oppose immune function (e.g. superoxide dismutase - inactivates immune cells)

Invasion and Intracellular Pathogens

• How microbes invade the body:
  • 1. Bind to surface
  • 2. Invade and go through tissues to get to underlying surfaces and penetrate the mucosal layer
• 3 Properties aid invasion:
  • 1. Secreted bacterial enzymes (disrupt and destroy tissues and protein structures)
  • 2. Antiphagocytic capsule (prevents uptake)
  • 3. Toxins that control uptake mechanisms
• 2 Ways intracellular bacteria carry out invasion:
  • 1. Phagocytosis (gets into cell, then escapes phagosome)
  • 2. Induces uptake by macropinocytosis or endocytosis (complex interactions)

Facultative and Obligate Intracellular Pathogens

• Facultative pathogens: Can survive in multiple niches, including the host
• Obligate pathogens: Require a host to fulfill their life cycle
• Examples of facultative intracellular pathogens:
  • 1. Mycobacterium tuberculosis
  • 2. Legionella pneumophila
  • 3. Listeria monocytogenes
  • 4. Salmonella typhimurium
  • 5. Shigella flexneri (dysentery)
  • 6. Brucella abortus (congenital fever)
• Examples of obligate intracellular bacterial pathogens:
  • 1. Mycobacterium leprae (leprosy)
  • 2. Chlamydiaceae (common STD)
  • 3. Rickettsia prowazekii (typhus)

Chlamydia

• Dimorphic: Exists in 2 forms:
  • Elementary body (EB) - infectious, but inert
  • Reticulate body (RB) - not infectious, metabolically active
• How the 2 forms of chlamydia work:
  • 1. EB attaches to phagocyte and is ingested
  • 2. Phagosome fusion occurs with the EB
  • 3. The EB reorganises to RB
  • 4. RB multiplies as it is metabolically active
  • 5. Condensation of RB to EB occurs (as this is infectious)
  • 6. Infectious EB is released

Rickettsiae

• Obligate intracellular bacteria
• Mechanism of Rickettsiae:
  • 1. Entry into cell
  • 2. Escapes phagosomes
  • 3. Into cellular environment
  • 4. Grows and replicates
  • 5. Grows actin tail
  • 6. Escapes through cell membrane with use of actin tail provided by the host

Obligate Intracellular Bacteria

• 9 Features:
  • 1. Long generation time
  • 2. Small size with small genome
  • 3. Requires exogenous energy supply
  • 4. May infect non-phagocytic cells
  • 5. Protected from lysosomal degradation
  • 6. Uses own expression and replication mechanisms
  • 7. No environmental reservoir
  • 8. Cannot be grown by standard bacterial culture techniques
  • 9. Difficult to study

Advantages of Intracellular Infection

• Immune evasion
• Carriage around body via the host cell
• Obtain nutrients from host
• Smaller genome size

Pyogenic Inflammation

• Rapid inflammation leading to:
  • 1. Cytokine induction
  • 2. Recruitment of neutrophils and macrophages
  • 3. Opsonisation and bacterial killing
• Caused by lipopolysaccharide (Pathogen Associated Molecular Pattern - PAMPs)
• Examples of bacteria that can cause pyogenic inflammation:
  • 1. Streptococcus pyogenes
  • 2. S. pneumoniae
  • 3. Staphylcoccus aureus

Granulomatous Inflammation

• Macrophage and T cell response to Mycobacterium tuberculosis
• A granuloma is formed to 'sequester' the pathogen, which limits spread

Infections

• An infection is a process of tissue invasion by microorganisms, where they multiply in the body of the host to cause disease.
• There are 4 types of infections:
  • Bacterial
  • Fungal
  • Viral
  • Parasitic
• Cross-infection is the transmission of infection between patients and healthcare professionals.

Viral Infections

• Examples of viral infections:
  • CMV
  • Hepatitis virus
  • HSV1 and 2
  • HIV
  • Measles
  • Mumps
  • Influenza
  • Rubella
  • Adenovirus

Herpes Simplex (HSV)

• HSV1 is spread by infected saliva.
• HSV2 is spread by sexual contact.
• Incubation period of HSV: 2-12 days.
• Clinical features of HSV:
  • Orolabialis infection (oral herpes)
  • Sore throat, fever
  • Vesicles on pharynx, buccal mucosa, gingiva, and tongue
  • Lymphadenopathy (enlargement of lymph nodes)
  • Recurrence
• Infections associated with HSV1 and HSV2:
  • HSV-1 and HSV-2: skin infections, herpetic whitlow
  • HSV-1: eye infections, blindness can occur
  • HSV-2: genital/anal infections
• Complications of HSV:
  • Encephalitis (affects temporal lobes)
  • Neonatal (mortality rate is 60% for newborns, c-section may be needed)
  • Erythema multiforme (skin reaction)
  • Eczema herpeticum (virus affects a large part of the skin)
• Treatment of HSV:
  • Acyclovir
  • Valacyclovir

Herpes Zoster

• Herpes zoster is caused by the reactivation of the varicella zoster virus.
• Clinical features of Herpes zoster:
  • Radicular pain (pain that radiates from your back and hip into your legs through the spine)
  • Hyperaesthesia (increase of sensitivity) of overlying skin
  • Rash
  • Erythema caused by inflamed blood capillaries
  • Oral, palatal, or pharyngeal involvement if the Trigeminal nerve is affected
• Complications of Herpes zoster:
  • Post-herpetic neuralgia
  • Meningitis (neurological)
• Treatment of Herpes zoster:
  • Acyclovir
• Complication that treatment has no effect on:
  • Post-herpetic neuralgia

Infectious Mononucleosis

• Infectious mononucleosis is caused by the Epstein-Barr virus.
• Incubation period: 4-14 days.
• Clinical features of infectious mononucleosis:
  • Anorexia, malaise, fever
  • Sore throat
  • Cervical lymphadenopathy (swelling of lymph nodes)
  • Macular rash due to ampicillin
  • Palatal petechiae
  • Palpable spleen
  • Jaundice in 10% of cases
• Complications of infectious mononucleosis:
  • Hepatitis
  • Respiratory obstruction
  • Ruptured spleen
• Diagnosis of infectious mononucleosis:
  • Monospot test

Chicken Pox

• Chicken pox is caused by the varicella zoster virus.
• Incubation period: 14-16 days.
• Clinical features of chicken pox:
  • Rash that starts on scalp/trunk then spreads to limbs and face
  • Vesicles dry and crust
  • Pruritis (itchiness)
  • Shallow ulcers on mucous membranes
• Complications of chicken pox:
  • Cellulitis/impetigo
  • Pneumonia
  • Acute cerebellar ataxia, Reye's syndrome (neurological)
  • Congenital abnormalities
• Treatment of chicken pox:
  • Antihistamines
  • Acyclovir (for severe cases/complications)

Mumps

• Mumps is caused by the paramyxovirus (RNA).
• Incubation period: 16-21 days.
• Clinical features of mumps:
  • Asymptomatic in 40%
  • Fever, malaise
  • Enlargement of 1/both parotids
  • Earache and displacement of earlobe
  • Partoid papillae inflamed
  • Difficulty in swallowing
  • Submandibular glands may be affected
• Complications of mumps:
  • Neurological: aseptic meningitis, encephalitis
  • Orchitis (common in post-puberty, 20-25%)
  • Non-parotid mumps: ovaries, thyroid, pancreas, breasts
• Treatment of mumps:
  • Good oral hygiene
  • Bed rest

Haematopoiesis and Cell Lines

• 7 cell lines arise from haematopoiesis:
  • Red blood cells: transport O2 from lungs to tissues
  • Neutrophils: chemotaxis, phagocytosis, killing of phagocytosed cells
  • Eosinophils: neutrophil functions + antibody-dependent damage to parasites, immediate hypersensitivity
  • Basophils: immediate hypersensitivity, modulate inflammatory response via proteases and heparin
  • Monocytes and macrophages: chemotaxis, phagocytosis, killing of micro-organisms, antigen presentation and release of IL-1 and TNF
  • Platelets: primary haemostasis (adhere to subendothelial connective tissue)
  • Lymphocytes: immune response and haemopoietic growth factors

Haemoglobin Levels and Anaemia

• Haemoglobin levels:
  • Children (6 months-6 years): 110-145 g/L
  • Children (6 years-14 years): 120-155 g/L
  • Adult males: 130-170 g/L
  • Adult females: 120-155 g/L
  • Pregnant females: 110-140 g/L
• Anaemia: reduction in haemoglobin levels below the reference range for age and sex of the individual
• Rate at which anaemia develops dictates symptoms and signs

Symptoms and Signs of Anaemia

• Symptoms:
  • Lassitude
  • Fatigue
  • Dyspnoea on exertion
  • Palpitations
  • Headache
  • Chest pain
• Signs:
  • Pallor
  • Tachycardia
  • Wide pulse pressures
  • Systolic flow murmurs
  • Congestive cardiac failure

Mechanisms of Anaemia Development

• 5 mechanisms:
  • Blood loss
  • Decreased red cell lifespan (haemolytic)
  • Impairment of red cell formation
  • Pooling and destruction of RBCs in spleen
  • Increased plasma volume (pregnancy)

Morphology of Anaemia

• 3 types:
  • Microcytic (small): Iron deficiency, Thalassaemias
  • Normocytic (normal): Acute blood loss, Anaemia of chronic disease, Chronic renal failure
  • Macrocytic (big): Alcoholism, Folate deficiency, Vitamin B12 deficiency, Drugs

Iron Deficiency Anaemia

• Most common cause of microcytic anaemia worldwide
• Iron tightly managed in the body due to toxicity
• 3 mechanisms of iron deficiency development:
  • Poor dietary intake
  • Malabsorption
  • Increased loss of iron
• 6 manifestations of iron deficiency:
  • Koilonychia
  • Angular chelitis
  • Atrophic glossitis
  • Recurrent oral ulceration
  • Burning mouth
  • Oesophageal web (Plummer-Vinson / Patterson-Brown Kelly syndrome)

Management of Iron Deficiency Anaemia

• Blood film and iron studies
• Address underlying cause
• Oral supplementation (ferrous sulphate 200mg x3 a day for 3 months)
• Parenteral available (fever, arthropathy, anaphylaxis)
• Blood transfusion (only in severe compromise)

Other Causes of Microcytic Anaemia

• Thalassaemias: inherited blood disorder, less haemoglobin than normal

Normocytic Anaemia

• Associated with:
  • Chronic inflammatory/connective tissue (rheumatoid arthritis)
  • Chronic infections (tuberculosis)
  • Chronic renal disease (due to reduction in erythropoietin)
  • Malignancies (bone marrow infiltration)

Macrocytic Anaemia

• 2 divisions:
  • Megaloblastic erythropoiesis: abnormal red cell development due to disordered DNA synthesis
  • Normoblastic erythropoiesis: normal red cell maturation
• Megaloblastic anaemia: Macrocytic anaemia due to:
  • Folate (vitamin B9) deficiency
  • Vitamin B12 deficiency

Folate and Vitamin B12 Deficiencies

• Causes of deficiencies:
  • Folate: inadequate intake, malabsorption, increased requirement, increased loss, drugs
  • Vitamin B12: inadequate intake, inadequate secretion of intrinsic factor, inadequate release from food, diversion of dietary B12, malabsorption
• Clinical features:
  • Generic symptoms and signs of anaemia
  • Occasional mild jaundice
  • Glossitis
  • Oral ulceration
  • Peripheral neuropathy (loss of proprioception and vibration sense) (Vitamin B12 only)
  • Demyelination with subacute combined degeneration of spinal cord (Vitamin B12 only)
  • Dementia (Vitamin B12 only)

Management of Megaloblastic Anaemia

• Investigations: Blood film, Serum folate and B12
• Address underlying cause
• Oral supplementation (never folate only if B12 level not known)
• Parenteral vitamin B12 (IM) required in pernicious anaemia

Normoblastic Macrocytosis

• 4 causes:
  • Alcohol excess
  • Liver dysfunction
  • Hypothyroidism
  • Drugs (methotrexate, azathioprine)

Haemolytic Anaemia

• 2 types:
  • Congenital
  • Acquired
• Congenital haemolytic anaemia:
  • Membrane defects
  • Enzyme defects (G6DP deficiency)
  • Globin defects
• Acquired haemolytic anaemia:
  • Immune (IgG coated red cells)
  • Non-immune (mechanical trauma, infections, drugs)

Clinical Features of Haemolytic Anaemia

• Pallor
• Jaundice (due to elevated bilirubin)
• Splenomegaly (enlargement of the spleen)
• Expansion of erythropoiesis leading to bone deformities (frontal bossing) and pathological features